Original Article
Immunohistologic Abnormalities of the Microfibrillar-Fiber System in the Marfan Syndrome
N Engl J Med 1990; 323:152-159July 19, 1990
- Abstract
- Abstract
Background.
Indirect-immunofluorescence studies of skin and cultured dermal fibroblasts from patients with the Marian syndrome demonstrate apparent deficiency of one element of connective tissue — the microfibrillar-fiber system — in assays using specific antibodies against fibrillin, a major microfibrillar protein. This study was designed to test whether these immunostaining abnormalities are consistent and diagnostic features of the disease.
Methods.
We studied patients with either the Marfan syndrome or various other inherited connective-tissue disorders and normal subjects according to a single-blind protocol in which coded samples of skin, fibroblast cultures, or both were analyzed without knowledge of the clinical diagnosis and classified as "Marian" or "non-Marfan" before the sample codes were broken.
Results.
Of the 27 patients with the Marfan syndrome, 24 were correctly identified by the decreased content of microfibrillar fibers in their skin, cultured fibroblasts, or both; in contrast, 19 of 25 patients with other heritable disorders of connective tissue and all 13 normal subjects were correctly classified as "non-Marfan" by these assays (P<0.001).
Conclusions.
These results document consistent, relatively specific abnormalities of microfibrillar fibers in the Marfan syndrome. The biomechanical incompetence of these structural elements, due to quantitative or qualitative abnormalities, may account for the pleiotropic clinical manifestations of the disease. Therefore, various defects in the expression, structure, assembly, or degradation of the constituent structural glycoprotein (or glycoproteins) of microfibrils may be implicated in the causation of the Marfan syndrome. (N Engl J Med 1990; 323: 152–9.)
Article Activity
- Article
THE Marfan syndrome is an inherited disorder of connective tissue characterized by pleiotropic manifestations in many organs, including the eyes, heart, aorta, skeleton, skin, and lung. Life expectancy is reduced by one third, on average, because of emergent cardiovascular complications. The clinical features and phenotypic variability of this dominantly inherited disease have been described at length.1 2 3 4 Diagnosis is now based entirely on clinical evaluation and family history.5
The cause of the Marfan syndrome is not known. Defects in collagen metabolism have long been suspected,6 7 8 9 but recent candidate-gene linkage studies have effectively excluded linked regulatory or primary structural defects of the major fibrillar collagens, Types I, II, and III.10 11 12 13 Defects in elastin have also been suspected, in view of the fragmentation of elastic tissue in the tunica media of the aorta,14 other arteries,15 and skin,16 biochemical studies of aortic elastin,17 and the increased urinary excretion of elastin metabolites that occurs in patients.18 The absence of common restriction-site polymorphisms linked to the elastin gene has precluded extensive studies, but in several families the possibility of linkage has been excluded. 19 , 20 Attention has focused as well on the overproduction of hyaluronic acid by cultured fibroblasts from patients with the Marfan syndrome,21 , 22 a consistent finding of uncertain importance.
Microfibrillar fibers make up a discrete, widely distributed, and pleiomorphic fiber system in human tissues. When visualized by electron microscopy, the fibers appear as linear bundles containing many individual microfibrils,23 which are thread-like filaments with a tubular cross-section and an average diameter of 10 to 12 nm. Microfibrillar fibers form a variety of structures, including long rods, sheets or lamellae, and meshworks.24 , 25 Substantial evidence indicates that the fibers serve as the scaffolding for the deposition of elastin during elastogenesis,24 , 26 and in many tissues the fibers become incorporated, in whole or in part, into elastic structures. In the aorta, for example, concentric lamellae of microfibrillar fibers are completely invested with elastin, producing the concentric rings of elastin seen in mature tunica media. In skin, a continuous meshwork of fibers extends from the dermal-epidermal basement membrane into the reticular dermis, but only limited deeper portions are invested with elastin and become recognizable elastic fibers.27
Microfibrillar fibers are considered integral components of elastic elements,24 , 26 but it is now apparent that such fibers are much more widely distributed than elastin. They have been visualized by immunolocalization studies in skin, tendon, cartilage, muscle, kidney, perichondrium, periosteum, blood vessels, pleura, dura mater, and ciliary zonules of the ocular lens.28 29 30
The molecular composition of microfibrils is incompletely understood. Recently, fibrillin, a 350-kd glycoprotein, was partially characterized and specifically immunolocalized to microfibrils in a number of human tissues with the use of several monoclonal antibodies.30 These same antibodies reacted avidly with ciliary zonules, which are devoid of elastin and almost exclusively composed of microfibrillar fibers.31 Because ectopia lentis in the Marfan syndrome may result from structural or functional abnormalities of zonules, McKusick1 suggested that understanding the common factor in aortic media and the ciliary zonules might reveal the basic defect. To determine whether microfibrillar fibers represent this common factor, we conducted preliminary studies32 32 34 on skin and fibroblasts from patients with the Marfan syndrome, using monoclonal antibodies against fibrillin as specific probes to examine the array of microfibrillar fibers. The results indicated deficiencies in the amount and distribution of microfibrillar fibers. To verify these findings and test the hypothesis that such abnormalities are a consistent and distinguishing feature of the Marfan syndrome, a single-blinded study was organized; in this article, the observed immunostaining abnormalities and the results of the study are presented.
Methods
Study Design
The study followed a single-blind protocol and included 65 persons: patients with either the Marfan syndrome or various other heritable disorders of connective tissue, and normal subjects. All were examined at the Johns Hopkins Hospital by one of us and classified according to rigid diagnostic criteria.5 Three of the normal subjects were found to have mild joint laxity at one pair of joints, and one had slight scoliosis, but none had evidence of a generalized disorder of connective tissue.
Tissue Specimens
After informed consent had been obtained, a 4-to-5-mm full-thickness punch-biopsy specimen of skin was taken from the posteromedial upper arm, an area not exposed to the sun. The biopsy specimen was divided; the larger portion was frozen and stored in hexane at −20°C for tissue sectioning, and the smaller portion was placed in mediums for cell culture. Different coding systems were used for the tissue- and cell-culture portions to ensure that subsequent analyses would be performed without knowledge of the clinical diagnosis or of the correspondence between the two samples from the same person. All specimens were analyzed in Portland, Oregon.
Skin Immunofluorescence Studies
Cryosections of skin (15 μm) were cut on a Leitz 1720 Kryostat, air-dried on poly-L-lysine-coated glass slides, fixed for 10 minutes in acetone at -20°C, washed with phosphate-buffered saline, and incubated with murine monoclonal antibody at room temperature for one to two hours. After washing with phosphate-buffered saline, the sections were incubated for 30 minutes with fluorochrome-conjugated antimouse IgG antiserum as secondary antibody. We used fluorescein isothiocyanate-conjugated antiserum initially, but emissions attributable to this fluor could not be reliably distinguished from the autofluorescence of elastic fibers. Therefore, goat antimouse IgG conjugated with phycoerythrin (Biomeda) was used for most studies. Sections were washed with phosphate-buffered saline and then counterstained with 0.00025 percent propidium iodide (Biomeda), a fluorescent nuclear stain, for 10 minutes, washed carefully with saline solution and cover slips applied with Gel/Mount (Biomeda). The sections were viewed on a Zeiss Photoscope III equipped with epifluorescent illumination, a fluorescein isothiocyanate excitation filter, and a barrier filter allowing the passage of wavelengths longer than 520 nm. The maximal emission of phycoerythrin is 575 nm (yellow-gold), and that of propidium iodide is 639 nm (pink-red); both fluors were visualized simultaneously. Photographs were taken with high-speed Ektachrome color film (Kodak); all exposures lasted 15 seconds to permit comparison of the intensity of fluorescence.
Samples of normal adult skin or neonatal foreskin were typically processed in parallel with unknown samples as positive controls. Negative controls included the substitution of an irrelevant monoclonal antibody or saline for the first or second antibody or the use of culture mediums lacking antibody, in studies using monoclonal antibodies in cell-culture supernatants.
To investigate possible antigenic masking, air-dried cryosections of skin were digested with chondroitin ABC lyase before fixation (Miles Laboratories; 0.0125 unit in 50 μl of 100 mM TRIS-acetate buffer [pH 7.6] per section for 90 minutes at 37°C35), hyaluronidase (Worthington; 800 units in 100 μl of 0.1 M phosphate buffer [pH 5.3] for 20 minutes at room temperature30), or elastase (Worthington; 0.01 percent in 0.067 M TRIS–hydrochloric acid [pH 8.8] for 20 minutes at room temperature30). After digestion, the sections were stained with monoclonal antibody as described above.
Fibroblast Immunofluorescence Studies
Skin fibroblast cultures were established and maintained in Dulbecco's modified Eagle's medium containing 10 percent fetal-calf serum and antibiotics, according to standard procedures. Cells (2.5×105) were plated onto each chamber (1 cm2) of four-chamber glass or plastic microscope slides (Miles Laboratories) and incubated in 1 ml of medium for 48 hours. The resultant hyperconfluent multilayers were fixed and stained as described above. Typically, two chambers of each slide served as controls for primary and secondary antibodies. Foreskin fibroblasts and, frequently, normal adult dermal fibroblasts were used as positive controls and processed in parallel in all studies. It was not possible to investigate possible antigenic masking in cell cultures, since enzymatic digestion (described above) caused the detachment of the fibroblast multilayers.
Monoclonal Antibodies
Murine monoclonal antibodies specific for various human connective-tissue proteins were used. In early studies, antibodies against human Type III,36 IV,37 VI,38 and VII39 collagen were used. Two antibodies (F2 and 201) specific for fibrillin, a major protein of microfibrils,30 were used; these IgG antibodies recognize different epitopes within the fibrillin molecule, as judged by their reactivity with different cyanogen bromide (unpublished data) or pepsin40 cleavage fragments of fibrillin and cross-species reactivity (201 antibody) as compared with their specificity for human fibrillin (F2 antibody). These antibodies are also useful for the immunoprecipitation and immunoblotting of fibrillin from fibroblast culture mediums.30 All antibody-stained samples were examined independently by two observers and classified as either "Marfan" or "non-Marfan" before the codes were broken.
Statistical Analysis
Probabilities were calculated with Fisher's exact test (two-tailed) for two-by-two or two-by-three tables with use of SPSS-X software. The results of the immunohistologic studies of patients with the Marfan syndrome were compared with the patients' phenotypic manifestations by Fisher's exact chi-square test.
Results
Immunofluorescence Studies
Indirect immunofluorescence of normal human skin with each of the monoclonal antibodies (F2 and 201) against fibrillin produced a characteristic and highly reproducible immunostaining pattern (Fig. 1Figure 1
Fluorescence Photomicrographs of 15-μm Cryosections of Skin from a Healthy 32-Year-Old Man and a 37-Year-Old Man with the Marfan Syndrome (×210).A and 1B). The dermal-epidermal junction was brightly stained and appeared as a nearly continuous band paralleling the basement membrane. Subjacent to this band was a region of relative lucency through which linear strands of fibers descended. The papillary dermis was richly invested with a branching meshwork of fibers of various diameters that often coalesced in irregular structures and was particularly prominent around skin appendages. Many of the larger fibrous bands in this region paralleled the plane of the dermal-epidermal junction (Fig. 1A). Deeper jn the reticular dermis, the fine fibrous pattern became attenuated and dominated by distinctly larger, undulating fibers of various lengths and diameters (Fig. 1B). In photoquenching experiments in which the phycoerythrin fluorescence was destroyed, such fibers had the greenish autofluorescence of elastin bundles, indicating that the most prominent microfibrillar fibers in this region were associated with elastic fibers.In contrast, many but not all patients with the Marfan syndrome had qualitative and quantitative alterations in the staining pattern of microfibrillar fibers in skin (Fig. 1C and 1D). The apparent overall intensity of staining was often diminished in the dermis. At the dermal—epidermal junction, discontinuities were often seen along the basement membrane, the apparent content of fibrous material was decreased in the papillary dermis, and the elastin bundles of the reticular dermis were irregularly associated with fluorescence. Identical results were obtained with both the antifibrillin monoclonal antibodies.
To explore the possibility of antigenic masking, sections of skin were digested with chondroitin ABC lyase or hyaluronidase before staining, but this did not alter the immunostaining pattern or intensity in skin from either patients or normal subjects. However, digestion with elastase before the application of either antifibrillin antibody reproducibly increased the intensity of immunofluorescence slightly in skin from both patients with the Marfan syndrome and normal subjects, but did not alter the relative differences.
The patterns of immunofluorescent staining with anticollagen monoclonal antibodies (against Types III, IV, VI, and VII collagen) were identical in skin from patients with the Marfan syndrome and normal subjects (data not shown).
Hyperconfluent normal human fibroblasts synthesized, secreted, and assembled a prominent network of extracellular fibrous material reactive with both the antifibrillin antibodies (Fig. 2Figure 2
Hyperconfluent Multilayers of Dermal Fibroblast from a Normal Subject (Panel A) and a Patient with the Marfan Syndrome (Panel B) (×300).A). This phenomenon was dependent on both time and cell density, and the heaviest accumulations of fibrous meshwork were associated with the largest number of cells. The standard 48-hour assay was highly reproducible and independent of cell-passage number from 1 to 15 passages.In the same two-day assay, fibroblast cultures from patients with the Marfan syndrome showed a diminished accumulation of fibrous material staining with antifibrillin antibodies. The relative amount of staining varied among the patients, but in most the decrease in staining was striking, there being only occasional, widely scattered patches of wispy fibrils despite large numbers of cells in the hyperconfluent multilayers (Fig. 2B). Both the antifibrillin antibodies gave similar results.
Single-Blind Study
Table 1Table 1
Phenotypic Features, Relative Severity of Disease, and Results of Immunofluorescence Studies in 27 Patients with the Marfan Syndrome.* lists the clinical features, relative severity of disease, and immunohistologic diagnosis of the 27 patients with the Marfan syndrome who were studied. The average age of the 21 male and 6 female patients was 29.2 years (range, 5 to 49). Eight patients were first-degree relatives (three father-son pairs and one mother-daughter pair). The results of the immunofluorescence studies are summarized in Table 2Table 2
Results of Immunofluorescence Studies in Patients with the Marfan Syndrome.*. According to the criteria of characteristic immunohistologic abnormalities of skin, fibroblast culture, or both, 24 of the 27 patients were correctly identified in a blinded fashion as having the Marfan syndrome.Of the 14 patients with the Marfan syndrome in whom both skin and fibroblast assays were performed, 13 (93 percent) were correctly identified by abnormal results on one (5 patients) or both (8 patients) assays. In the five patients in whom the results of the two assays did not agree, four had skin immunostaining within the normal range but clearly abnormal fibroblast immunofluorescence. A five-year-old girl, the youngest patient studied, had abnormal skin immunostaining but normal fibroblast immunofluorescence. Finally, one patient had normal results in both assays in two independent biopsies and was thus misdiagnosed as not having the Marfan syndrome. This patient had typical features of the syndrome and a positive family history, but was the only patient lacking both striae atrophicae and joint hypermobility.
Considering the results of skin immunofluorescence studies alone, 16 of 23 patients (70 percent) with the Marfan syndrome were correctly identified, whereas 7 (30 percent) were misclassified as not having the syndrome. In comparison, 16 of 18 patients (89 percent) with the Marfan syndrome studied by fibroblast immunostaining were given correct diagnoses with this assay alone. Although the results of skin and fibroblast immunofluorescence studies were not statistically different, fibroblast immunostaining appeared to be more sensitive and reliable.
A total of 13 normal subjects were studied. The average age of the five male and eight female subjects was 31.8 years (range, 5 to 65). Six of the subjects underwent immunohistologic studies of skin alone, and seven underwent both skin and fibroblast immunofluorescence studies. All of the subjects were correctly identified as not having the Marfan syndrome in all studies.
Twenty-five patients with a connective-tissue disease other than the Marfan syndrome were also studied. The average age of the 15 male and 10 female patients was 31.9 years (range, 3 to 54). Seventeen of the patients underwent both skin and fibroblast immunofluoresence studies, and eight underwent one or the other. Eighteen patients were correctly identified as not having the Marfan syndrome. Among them were five with mitral-valve-prolapse syndrome, five with Ehlers-Danlos syndrome, two with pseudoxanthoma elasticum, two with annuloaortic ectasia, and one each with arterial ectasia, mandibuloacral dysplasia, the Stickler syndrome (hereditary arthroophthalmopathy), and the Job syndrome. Seven patients were found to have alterations in immunofluorescence similar to those in patients with the Marfan syndrome on one or both assays, and six of these were misclassified as having the Marfan syndrome. The clinical diagnosis and results of immunostaining for these patients are shown in Table 3Table 3
Diagnosis and Immunostaining Results in Seven Patients Misclassified as Having the Marfan Syndrome.. A child with congenital cutis laxa had a greatly diminished network of microfibrillar fibers in the skin; however, digestion with elastase resulted in the unmasking of a normal pattern of immunofluorescence, a result in distinct contrast to the findings in samples from the patients with the Marfan syndrome. The results of immunostaining of fibroblast cultures from this child were normal, as was the staining pattern of skin and fibroblast cultures of the child's unaffected parents. On the basis of these observations, the patient was classified as not having the Marfan syndrome.Statistical comparison of the results by Fisher's exact test produced significant differences. The results in the patients with the Marfan syndrome differed from those in patients with other connective-tissue diseases (P<0.0005), normal subjects (P<0.0003), and both control groups (P<0.00001). The two control groups did not differ significantly. For the patients with the Marfan syndrome, no significant association was found between the results of skin or fibroblast immunostaining and the presence or absence of specific phenotypic manifestations or the relative severity of disease as listed in Table 1.
Discussion
We found that indirect-immunofluorescence studies of skin and dermal fibroblasts using monoclonal antibodies against fibrillin, a major microfibrillar glycoprotein, distinguished patients with the Marfan syndrome from normal subjects and most patients with other heritable connective-tissue disorders. The sensitivity for detecting the Marfan syndrome was 89 percent. These results should be viewed in the light of the known clinical variability and probable heterogeneity of this dominantly inherited disease, and may reflect a common pathogenetic mechanism of the Marfan syndrome involving qualitative and quantitative abnormalities of microfibrillar fibers. The results also undoubtedly reflect the selection of patients with unequivocal clinical manifestations of the Marfan syndrome and the exclusion of the much larger group of patients in whom this diagnosis is entertained but uncertain.41 We have studied few patients in this larger group and do not yet know whether similar abnormalities will be observed.
There were no false positive diagnoses of the Marfan syndrome in 13 normal subjects. In nonblinded family studies, an additional 13 unaffected first-degree relatives of patients with the Marfan syndrome had normal immunostaining of skin and fibroblast cultures42; in blinded studies, 10 further unaffected relatives had normal immunostaining of skin (Pyeritz RE et al.: unpublished data). Thus, 36 phenotypically normal people have had uniformly normal results.
Among the results in the patients with other connective-tissue diseases, several deserve comment. First, those with diseases whose relation to the Marfan syndrome is uncertain — mitral-valve-prolapse syndrome and annuloaortic ectasia — had normal results, suggesting that at least some patients with these phenotypes have disorders distinct from the Marfan syndrome. Normal immunostaining results have recently been reported in a kindred with familial aortic dissection without other stigmata of the Marfan syndrome43 and in a kindred with severe myxomatous valvular disease.44 Second, except for a patient with homocystinuria, those with abnormal immunostaining had diseases clinically dissimilar to the Marfan syndrome, and at least some of these disorders (pseudoxanthoma elasticum and cutis laxa) involved the elastic-fiber system but not necessarily microfibrillar fibers.
We found three patterns of immunofluorescence in the patients with the Marfan syndrome: about 70 percent had abnormal skin and fibroblast-culture immunostaining; about 25 percent had ambiguous or normal skin immunostaining but abnormal fibroblast-culture immunostaining; and one patient had diminished skin immunostaining but normal fibroblast-culture immunostaining. To date, 2 of 44 patients with the Marfan syndrome have had this third pattern. These patterns have been confirmed in studies documenting uniform cosegregation of abnormalities on immunofluorescence with patients with the Marfan syndrome in families, but not with their unaffected relatives; notably, the specific pattern was identical for all affected patients within a given kindred.42 To date, no differences in the phenotypic manifestations of the Marfan syndrome have been correlated with these differing results of immunostaining. The cause of these patterns is unknown but presumably reflects underlying molecular heterogeneity.
Three patients with the typical Marfan syndrome were misclassified. Of these patients, two were studied only by skin immunostaining, an assay whose results are normal in about one quarter of patients with the Marfan syndrome. In the other misdiagnosed case, the results of skin and fibroblast-culture immunostaining were consistently normal, an anomalous and thus far unexplained situation.
The results of immunostaining in skin and fibroblasts could be due to a Marfan syndrome-specific macromolecule masking the antigenic binding sites on microfibrils and preventing the access of antibody. This possibility seems remote, since the results with both the monoclonal antibodies, each directed against different epitopes of the fibrillin molecule, were similar. Further, attempts to "unmask" antigenic sites by enzyme digestion with chondroitin ABC lyase, hyaluronidase, and elastase were unsuccessful. With respect to the elastase, the successful unmasking of antigenicity in a patient with cutis laxa serves as a positive control and suggests that elastin (or another protein digested by elastase) cannot be responsible for the results in the patients with the Marfan syndrome. Nevertheless, the formal possibility of antigenic masking, although unlikely, cannot be entirely excluded. A more likely explanation is a decreased net accumulation of microfibrillar fibers due to the deficient expression of a structural constituent of microfibrils, production of an abnormal constituent or inhibitor that interferes with the polymerization of microfibrils, absence of a factor that promotes fibrillogenesis, or augmented degradation.
Microfibrillar fibers are prominently distributed within the tissues affected in the Marfan syndrome, including ciliary zonules, aortic tunica media, pleura, dura mater, periosteum, perichondrium, and skin. Detailed information regarding the biomechanical properties and structural role or roles of such fibers within elastic fibers or in the absence of elastin is unavailable, although gross observations suggest that ciliary zonules have distinct elasticity.45 The consistent finding of stretched and occasionally broken zonular fibers in the ectopia lentis of patients with the Marfan syndrome4 argues that these microfibrillar fibers are functionally incompetent to resist normal stress and elongate progressively over time. This model provides a coherent and plausible explanation for the pleiotropic manifestations of the Marfan syndrome: for example, the progressive dilatation of the aortic root with the fragmentation of elastic lamellae of the tunica media, the striae atrophicae in skin, pulmonary bullae, and dural ectasia. Skeletal overgrowth may be due to diminished forces generated by the periosteal and perichondrial membranes that oppose bone growth.1
The studies reported here document consistent and relatively specific abnormalities of microfibrillar fibers in the Marfan syndrome that distinguish those with this disease from normal subjects and patients with various other disorders. Other data42 indicate that these abnormalities cosegregate with the Marfan phenotype in families but are not found in unaffected family members. Finally, similar studies in an unusual patient with unilateral Marfan syndrome have demonstrated a deficiency of microfibrils limited to the affected side of the body.46 These data, together with collateral information on the distribution and probable function or functions of microfibrillar fibers, serve to focus attention on this fiber system and its component microfibrils as potentially central to the causation and pathogenesis of the Marfan syndrome. A reasonable hypothesis is that molecular defects of one or more constituent structural glycoproteins produce deficient and functionally incompetent microfibrils. The composition of microfibrils is currently unclear but may include several other glycoproteins in addition to fibrillin, and at least some of these may be candidates for the defective gene product or products underlying the Marfan syndrome.
Supported by grants from the Shriners Hospitals of North America and the March of Dimes Birth Defects Foundation (1–1199) and by a General Clinical Research Center grant (RR-00722) from the National Institutes of Health.
Presented in part In abstract form (Clin Res 1987; 35:211 A, Am J Hum Genet 1987; 41:Suppl:A7, and Am J Med Genet 1989; 32:244).
We are indebted to Ms. Donna Gaudette and Ms. Eileen Roux for excellent technical assistance and to Dr. Eva Engvall for the monoclonal antibody to Type VI collagen.
Source Information
From the Portland Unit, Shriners Hospitals for Crippled Children (D.W.H., M.G., L.Y.S.), and the Departments of Biochemistry and Molecular Biology (D.W.H., M.G., L.Y.S.) and Medicine (D.W.H.), Oregon Health Sciences University, both in Portland; and the Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore (R.E.P.). Address reprint requests to Dr. Hollister at the Department of Pediatrics, University of Nebraska Medical Center, 600 S. 42nd St., Omaha, NE 68198–5430.
- References
References
1
McKusick VA. Heritable disorders of connective tissue. 4th ed. St. Louis: C.V. Mosby, 1972:61–223.
2
Pyeritz
Full Text | Web of Science | Medline3
Pyeritz RE. Marfan syndrome. In: Emery AEH, Rimoin DL, eds. Principles and practice of medical genetics. 2nd ed. New York: Churchill Livingstone (in press).
4
Maumenee
Medline5
Beighton
CrossRef | Web of Science | Medline6
Laitinen
CrossRef | Web of Science | Medline7
Scheck
Web of Science | Medline8
Boucek
Full Text | Web of Science | Medline9
Byers
CrossRef | Web of Science | Medline10
Tsipouras
Web of Science | Medline11
Dalgleish
CrossRef | Web of Science | Medline12
Ogilvie
Web of Science | Medline13
Francomano
CrossRef | Web of Science | Medline14
Derouette
Medline15
Takebayashi
Medline16
Tsuji
CrossRef | Web of Science | Medline17
Perejda
Medline18
Gunja-Smith
Web of Science | Medline19
Rosenbloom
Web of Science | Medline20
Huttunen
Web of Science21
Lamberg
CrossRef | Web of Science | Medline22
Appel
Web of Science | Medline23
Low
CrossRef | Web of Science | Medline24
Cleary
Medline25
Inoue
CrossRef | Web of Science | Medline26
Cleary EG. The microfibrillar component of the elastic fibers: morphology and biochemistry. In: Uitto J, Perejda AJ, eds. Connective tissue disease: molecular pathology of the extracellular matrix. New York: Marcel Dekker, 1987:55–81.
27
Cotta-Pereira
CrossRef | Web of Science | Medline28
Kewley
Web of Science | Medline29
Streeten
Web of Science | Medline30
Sakai
CrossRef | Web of Science | Medline31
Raviola
Medline32
Hollister 33
Hollister 34
Hollister
Web of Science35
Poole
CrossRef | Web of Science | Medline36
Keene
CrossRef | Web of Science | Medline37
Sakai
Web of Science | Medline38
Hessle
Web of Science | Medline39
Sakai
CrossRef | Web of Science | Medline40
Maddox
Web of Science | Medline41
Glesby
CrossRef | Web of Science | Medline42
Godfrey
Web of Science | Medline43
Nicod
CrossRef | Web of Science | Medline44
Rogan
CrossRef | Web of Science | Medline45
Streeten
Web of Science | Medline46
Godfrey
Web of Science | Medline
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Arie Y. Nemet, Ehud I. Assia, David J. Apple, Irina S. Barequet. (2006) Current Concepts of Ocular Manifestations in Marfan Syndrome. Survey of Ophthalmology 51:6, 561-575
CrossRef21
Alan T. Hirsch, Ziv J. Haskal, Norman R. Hertzer, Curtis W. Bakal, Mark A. Creager, Jonathan L. Halperin, Loren F. Hiratzka, William R.C. Murphy, Jeffrey W. Olin, Jules B. Puschett, Kenneth A. Rosenfield, David Sacks, James C. Stanley, Lloyd M. Taylor, Christopher J. White, John White, Rodney A. White, Elliott M. Antman, Sidney C. Smith, Cynthia D. Adams, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Raymond J. Gibbons, Jonathan L. Halperin, Loren F. Hiratzka, Sharon A. Hunt, Alice K. Jacobs, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel. (2006) ACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,
Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). Journal of the American College of Cardiology 47:6, e1-e192
CrossRef22
Hariyadarshi Pannu, Van Tran-Fadulu, Dianna M. Milewicz. (2005) Genetic basis of thoracic aortic aneurysms and aortic dissections. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 139C:1, 10-16
CrossRef23
Mario Di Silvestre, Tiziana Greggi, Stefano Giacomini, Alfredo Cioni, Georgios Bakaloudis, Francesco Lolli, Patrizio Parisini. (2005) Surgical Treatment for Scoliosis in Marfan Syndrome. Spine 30:20, E597-E604
CrossRef24
Jing Yu, Jeremy C. T. Fairbank, Sally Roberts, Jill P. G. Urban. (2005) The Elastic Fiber Network of the Anulus Fibrosus of the Normal and Scoliotic Human Intervertebral Disc. Spine 30:16, 1815-1820
CrossRef25
Gwenaëlle Collod‐Béroud, Catherine Boileau. 2004. Marfan Syndrome and Related Fibrillinopathies. , 761-765.
CrossRef26
Keitaro Isokawa, Hitomi Sejima, Osamu Shimizu, Yosuke Yamazaki, Koji Yamamoto, Yoshihisa Toda. (2004) Subectodermal microfibrillar bundles are organized into a distinct parallel array in the developing chick limb bud. The Anatomical Record 279A:2, 708-719
CrossRef27
Daniel P. Judge, Nancy J. Biery, Douglas R. Keene, Jessica Geubtner, Loretha Myers, David L. Huso, Lynn Y. Sakai, Harry C. Dietz. (2004) Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. Journal of Clinical Investigation 114:2, 172-181
CrossRef28
Peter H. Byers. (2004) Determination of the molecular basis of Marfan syndrome: a growth industry. Journal of Clinical Investigation 114:2, 161-163
CrossRef29
Anthony N Vomund, Stephen R Braddock, Gary F Krause, Charlotte L Phillips. (2004) Potential modifier role of the R618Q variant of proα2(I)collagen in type I collagen fibrillogenesis: in vitro assembly analysis. Molecular Genetics and Metabolism 82:2, 144-153
CrossRef30
Noe L. Charbonneau, Robert N. Ono, Glen M. Corson, Douglas R. Keene, Lynn Y. Sakai. (2004) Fine tuning of growth factor signals depends on fibrillin microfibril networks. Birth Defects Research Part C: Embryo Today: Reviews 72:1, 37-50
CrossRef31
Ryo Asaoka, Masaru Kato, Masahiro Suami, Yoshimasa Usami, Yoshihiro Hotta, Miho Sato. (2003) Chronic angle closure glaucoma secondary to frail zonular fibres and spherophakia. Acta Ophthalmologica Scandinavica 81:5, 533-535
CrossRef32
Maria Cristina Porciani, Letizia Giurlani, Andrea Chelucci, Guglielmina Pepe, Betti Giusti, Tamara Brunelli, Monica Attanasio, Pietro Martinucci, Rossella Fattori, Rosanna Abbatea, Gian Franco Gensini. (2002) Diastolic subclinical primary alterations in marfan syndrome and marfan-related disorders. Clinical Cardiology 25:9, 416-420
CrossRef33
Elisabetta Weber, Antonella Rossi, Raffaella Solito, Giovanni Sacchi, Margherita Agliano', Renato Gerli. (2002) Focal Adhesion Molecules Expression and Fibrillin Deposition by Lymphatic and Blood Vessel Endothelial Cells in Culture. Microvascular Research 64:1, 47-55
CrossRef34
Glenn Lipton, James Guille, S. Kumar. (2002) Journal of Pediatric Orthopedics 22:3, 302-307
CrossRef35
Glenn E. Lipton, James T. Guille, S. Jay Kumar. (2002) Surgical Treatment of Scoliosis in Marfan Syndrome: Guidelines for a Successful Outcome. Journal of Pediatric Orthopaedics 22:3, 302-307
CrossRef36
Iris Schrijver, Wouter I. Schievink, Maurice Godfrey, Fredric B. Meyer, Uta Francke. (2002) Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy. Journal of Neurosurgery 96:3, 483-489
CrossRef37
Bette J. Dzamba, Douglas R. Keene, Zenzo Isogai, Noe L. Charbonneau, Nevena Karaman-Jurukovska, Marcia Simon, Lynn Y. Sakai. (2001) Assembly of Epithelial Cell Fibrillins. Journal of Investigative Dermatology 117:6, 1612-1620
CrossRef38
Debra D. Wallis, Filemon K. Tan, Cay M. Kielty, Misty D. Kimball, Frank C. Arnett, Dianna M. Milewicz. (2001) Abnormalities in fibrillin 1-containing microfibrils in dermal fibroblast cultures from patients with systemic sclerosis (scleroderma). Arthritis & Rheumatism 44:8, 1855-1864
CrossRef39
Dianna M. Milewicz, Zsolt Urbán, Charles Boyd. (2000) Genetic disorders of the elastic fiber system. Matrix Biology 19:6, 471-480
CrossRef40
Francesco Ramirez. (2000) Pathophysiology of the microfibril/elastic fiber system: introduction. Matrix Biology 19:6, 455-456
CrossRef41
Alfonso Colombatti, Roberto Doliana, Simonetta Bot, Anna Canton, Maurizio Mongiat, Gabriella Mungiguerra, Stefano Paron-Cilli, Paola Spessotto. (2000) The EMILIN protein family. Matrix Biology 19:4, 289-301
CrossRef42
Andrea Herzka, Paul D. Sponseller, Reed E. Pyeritz. (2000) Atlantoaxial Rotatory Subluxation in Patients With Marfan Syndrome. Spine 25:4, 524
CrossRef43
Peter A. Cistulli, Colin E. Sulliva. (2000) Influence of Maxillary Morphology on Nasal Airway Resistance in Marfan's Syndrome. Acta Oto-laryngologica 120:3, 410-413
CrossRef44
S.M. Dridi, S. Ghomrasseni, D. Bonnet, Y. Aggoun, P. Vabres, C. Bodemer, S. Lyonnet, Y. de Prost, S. Fraitag, B. Pellat, D. Sidi, G. Godeau. (1999) Skin elastic fibers in Williams syndrome. American Journal of Medical Genetics 87:2, 134-138
CrossRef45
Stephen Westaby. (1999) Aortic dissection in Marfan’s syndrome. The Annals of Thoracic Surgery 67:6, 1861-1863
CrossRef46
A. Gigante, C. Chillemi, F. Greco. (1999) Journal of Pediatric Orthopedics 19:3, 283-288
CrossRef47
A. Gigante, C. Chillemi, F. Greco. (1999) Changes of Elastic Fibers in Musculoskeletal Tissues of Marfan Syndrome: A Possible Mechanism of Joint Laxity and Skeletal Overgrowth. Journal of Pediatric Orthopaedics 19:3, 283-288
CrossRef48
CAROLINE S. MAH, CARL J. VAUGHAN, CRAIG T. BASSON. (1999) Advances in the Molecular Genetics of Congenital Structural Heart Disease. Genetic Testing 3:2, 157-172
CrossRef49
Yuji Sugawara, Tadayuki Shimakura, Shin-ichiro Kihara, Satoshi Tanaka, Norihiko Saitoh, Mizuho Imamaki. (1998) A combination of reoperation for pseudoaneurysm following the Cabrol procedure and total aortic arch replacement in a patient with Marfan syndrome —A case with an aberrant right subclavian artery—. The Japanese Journal of Thoracic and Cardiovascular Surgery 46:10, 1041-1046
CrossRef50
P. S. Gutierrez, M. M. Reis, M. L. Higuchi, V. D. Aiello, N. A. G. Stolf, E. A. Lopes. (1998) Distribution of Hyaluronan and Dermatan/Chondroitin Sulfate Proteoglycans in Human Aortic Dissection. Connective Tissue Research 37:3-4, 151-161
CrossRef51
Saroj K. Parida, Vesna Martich Kriss, Bryan D. Hall. (1997) Hiatus/paraesophageal hernias in neonatal Marfan syndrome. American Journal of Medical Genetics 72:2, 156-158
CrossRef52
Cay M. Kielty, C. Adrian Shuttleworth. (1997) Microfibrillar elements of the dermal matrix. Microscopy Research and Technique 38:4, 413-427
CrossRef53
Björn Sonesson, Flemming Hansen, Toste Länne. (1997) Abdominal aortic aneurysm: A general defect in the vasculature with focal manifestations in the abdominal aorta?. Journal of Vascular Surgery 26:2, 247-254
CrossRef54
William R. Hobbs, Paul D. Sponseller, Arnold-Peter C. Weiss, Reed E. Pyeritz. (1997) The Cervical Spine in Marfan Syndrome. Spine 22:9, 983-989
CrossRef55
Kirk J Fleischer, MD, Hossein C Nousari, MD, Grant J Anhalt, MD, Christopher D Stone, MD, John C Laschinger, MD. (1997) Immunohistochemical Abnormalities of Fibrillin in Cardiovascular Tissues in Marfan’s Syndrome. The Annals of Thoracic Surgery 63:4, 1012-1017
CrossRef56
Caroline Hayward, David J. H. Brock. (1997) Fibrillin-1 mutations in Marfan syndrome and other type-1 fibrillinopathies. Human Mutation 10:6, 415-423
CrossRef57
Caroline Hayward, Mary E. Porteous, David J. H. Brock. (1997) Mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome: Report of 12 novel mutations. Human Mutation 10:4, 280-289
CrossRef58
Howard H. Steel. (1996) Protrusio Acetabuli: Its Occurrence in the Completely Expressed Marfan Syndrome and Its Musculoskeletal Component and a Procedure to Arrest the Course of Protrusion in the Growing Pelvis. Journal of Pediatric Orthopaedics704-718
CrossRef59
Howard H. Steel. (1996) Protrusio Acetabuli: Its Occurrence in the Completely Expressed Marfan Syndrome and Its Musculoskeletal Component and a Procedure to Arrest the Course of Protrusion in the Growing Pelvis. Journal of Pediatric Orthopaedics 16:6, 704-718
CrossRef60
M-V. BERTERETCHE, W. HORNEBECK, B. PELLAT, C. BLANCHET BARDON, G. GODEAU. (1995) Histomorphometric parameters and susceptibility to neutrophil elastase degradation of skin elastic fibres from healthy individuals and patients with Marfan syndrome, Ehlers-Danlos type IV, and pseudoxanthoma elasticum. British Journal of Dermatology 133:6, 836-841
CrossRef61
T. Rantamäki, M. Raghunath, L. Karttunen, L. Lönnqvist, A. Child, L. Peltonen. (1995) Prenatal diagnosis of marfan syndrome: Identification of a fibrillin-1 mutation in chorionic villus sample. Prenatal Diagnosis 15:12, 1176-1181
CrossRef62
K Hanséus, L-M Lundberg, G Björkhem, K Dahlbäck, I Hägerstrand, U Kristoffersson. (1995) Clinical and immunohistochemical findings in a case of neonatal Marfan syndrome. Acta Paediatrica 84:11, 1329-1332
CrossRef63
Takeshi Aoyama, Uta Francke, Cheryll Gasner, Heinz Furthmayr. (1995) Fibrillin abnormalities and prognosis in marfan syndrome and related disorders. American Journal of Medical Genetics 58:2, 169-176
CrossRef64
Cay M. Kielty, C.Adrian Shuttleworth. (1995) Fibrillin-containing microfibrils: Structure and function in health and disease. The International Journal of Biochemistry & Cell Biology 27:8, 747-760
CrossRef65
Mei Wang, John Mata, Christopher E. Price, Patrick L. Iversen, Maurice Godfrey. (1995) Prenatal and presymptomatic diagnosis of the marfan syndrome using fluorescence pcr and an automated sequencer. Prenatal Diagnosis 15:6, 499-507
CrossRef66
Yu-Sung Wu, Vicky L.H. Bevilacqua, Jeremy M. Berg. (1995) Fibrillin domain folding and calcium binding: significance to Marfan syndrome. Chemistry & Biology 2:2, 91-97
CrossRef67
Aslak Savolainen, Hannu Savolainen, Timo Savunen, Markku Kupari, Ilkka Kaitila, Markku Inberg, Severi Mattila. (1995) Results of Cardiovascular Surgery in the Marfan Syndrome: A Retrospective Study of 49 Patients. Scandinavian Cardiovascular Journal 29:1, 11-15
CrossRef68
Maurice Godfrey. (1994) From Fluorescence to the Gene: The Skin in the Marfan Syndrome.. Journal of Investigative Dermatology 103:s5, 58S-62S
CrossRef69
David J. Tilstra, Peter H. Byers. (1994) MOLECULAR BASIS OF HEREDITARY DISORDERS OF CONNECTIVE TISSUE. Annual Review of Medicine 45:1, 149-163
CrossRef70
C Beylot, MS Doutre, M Beylot-Barry, M Busquet. (1994) Les atteintes artérielles au cours des dysplasies héréditaires du tissu conjonctif. La Revue de Médecine Interne 15:3, 193-209
CrossRef71
David W. Wright, Christopher N. McDaniels, Somporn Swasdison, Mary Ann Accavitti, Pauline M. Mayne, Richard Mayne. (1994) Immunization with undenatured bovine zonular fibrils results in monoclonal antibodies to fibrillin. Matrix Biology 14:1, 41-49
CrossRef72
Caroline Hayward, Mary E. M. Porteous, David J. H. Brock. (1994) Identification of a novel nonsense mutation in the fibrillin gene (FBN1) using nonisotopic techniques. Human Mutation 3:2, 159-162
CrossRef73
Francesco Ramirez, Lygia Pereira, Hui Zhang, Brendan Lee. (1993) The fibrillin-marfan syndrome connection. BioEssays 15:9, 589-594
CrossRef74
CHERYL L. MASLEN, ROBERT W. GLANVILLE. (1993) The Molecular Basis of Marfan Syndrome. DNA and Cell Biology 12:7, 561-572
CrossRef75
Cheryll Gasner. (1993) The joining circles. American Journal of Medical Genetics 47:1, 136-142
CrossRef76
Paul McCullagh, Patrick J. Gallagher. (1993) Cardiovascular pathology. The Journal of Pathology 170:3, 321-325
CrossRef77
Cl. Beylot. (1993) Les atteintes artérielles au cours des dysplasies héréditaires du tissu conjonctif. La Revue de Médecine Interne 14:6, 469-472
CrossRef78
Roderick R. McInnes, Peter H. Byers. (1993) Biochemical genetics: examples of life after cloning. Current Opinion in Genetics & Development 3:3, 475-483
CrossRef79
M. Godfrey, P. A. Nejezchleb, G. B. Schaefer, D. J. Minion, Y. Wang, B. T. Baxter. (1993) Elastin and Fibrillin Mrna and Protein Levels in the Ontogeny of Normal Human Aorta. Connective Tissue Research 29:1, 61-69
CrossRef80
HARRY R. ALDRICH, ROBERT L. LABARRE, MARY J. ROMAN, STACEY E. ROSEN, MARIANE C. SPITZER, RICHARD B. DEVEREUX. (1992) Color Flow and Conventional Echocardiography of the Marfan Syndrome. Echocardiography 9:6, 627-636
CrossRef81
J.C. Parsons, Y. Hoffman, K.A. Potter, T.E. Besser. (1992) Normal elastin content of aorta in bovine Marfan syndrome. Experimental and Molecular Pathology 57:2, 145-152
CrossRef82
P.F. Pignatti, A.E. Turco. (1992) Tracking disease genes by reverse genetics. Journal of Psychiatric Research 26:4, 287-298
CrossRef83
B.Timothy Baxter, Gregory S. McGee, Vera P. Shively, Iain A.S. Drummond, Saryu N. Dixit, Mitsuo Yamauchi, William H. Pearce. (1992) Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. Journal of Vascular Surgery 16:2, 192-200
CrossRef84
Leena Peltonen, Katariina Kainulainen. (1992) Elucidation of the gene defect in Marfan syndrome Success by two complementary research strategies. FEBS Letters 307:1, 116-121
CrossRef85
Harry C. Dietz. (1992) Molecular biology of marfan syndrome. Journal of Vascular Surgery 15:5, 927-928
CrossRef86
Tsipouras, Petros, Del Mastro, Richard, Sarfarazi, Mansoor, Lee, Brendan, Vitale, Emilia, Child, Anne H., Godfrey, Maurice, Devereux, Richard B., Hewett, Duncan, Steinmann, Beat, Viljoen, Denis, Sykes, Bryan C., Kilpatrick, Michael, Ramirez, Francesco, the International Marfan Syndrome Collaborative Study* . (1992) Genetic Linkage of the Marfan Syndrome, Ectopia Lentis, and Congenital Contractural Arachnodactyly to the Fibrillin Genes on Chromosomes 15 and 5. New England Journal of Medicine 326:14, 905-909
Full Text87
P. Beighton, A. De Paepe, J. G. Hall, D. W. Hollister, F. M. Pope, R. E. Pyeritz, B. Steinmann, P. Tsipouras. (1992) Molecular nosology of heritable disorders of connective tissue. American Journal of Medical Genetics 42:4, 431-448
CrossRef88
Harry C. Dietz, Jorge M. Saraiva, Reed E. Pyeritz, Garry R. Cutting, Clair A. Francomano. (1992) Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. Human Mutation 1:5, 366-374
CrossRef89
Louise Sefton, Peter N. Goodfellow. (1992) The human genetic map. Current Opinion in Genetics & Development 2:3, 387-392
CrossRef90
R.Ellen Magenis, Cheryl L. Maslen, Leslie Smith, Leland Allen, Lynn Y. Sakai. (1991) Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1. Genomics 11:2, 346-351
CrossRef91
Kazuhito Hirata, Filippos Triposkiadis, Elizabeth Sparks, Juan Bowen, Charles F. Wooley, Harisios Boudoulas. (1991) The marfan syndrome: Abnormal aortic elastic properties. Journal of the American College of Cardiology 18:1, 57-63
CrossRef92
Harry C. Dietz, Reed E. Pyeritz, Bryan D. Hall, Ronald G. Cadle, Ada Hamosh, John Schwartz, Deborah A. Meyers, Clair A. Francomano. (1991) The Marfan syndrome locus: Confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics 9:2, 355-361
CrossRef93
Peter König, Robert Boxer, John Morrison, Beth Pletcher. (1991) Bronchial hyperreactivity in children with Marfan syndrome. Pediatric Pulmonology 11:1, 29-36
CrossRef94
Katariina Kainulainen, Leena Peltonen. (1991) Marfan Gene Discovered. Annals of Medicine 23:4, 395-396
CrossRef95
Corinne D. Boehm, Haig H. Kazazian. (1990) The molecular basis of genetic disease. Current Opinion in Biotechnology 1:2, 180-187
CrossRef96
Pyeritz, Reed E., . (1990) Marfan Syndrome. New England Journal of Medicine 323:14, 987-989
Full Text97
(1990) Fibrillin and Marfan's syndrome: a real clue?. The Lancet 336:8721, 973-974
CrossRef
