Correspondence

Absence of Dystrophin and Utrophin in a Boy with Severe Muscular Dystrophy

N Engl J Med 1994; 331:1162-1163October 27, 1994

Article

To the Editor:

Utrophin is an autosomally inherited protein encoded by chromosome 6 that is homologous to dystrophin and localized in normal adult muscle exclusively at neuromuscular junctions.1 No clinical disorder is recognized that relates to altered utrophin expression. Rather, utrophin levels have always been reported to increase in the absence of dystrophin in Duchenne's muscular dystrophy1-4 (and unpublished data) or of adhalin (50-kd dystrophin-associated glycoprotein) in severe autosomal recessive muscular dystrophy of childhood2 (and unpublished data). We describe a patient with defects of both dystrophin and utrophin in muscle fibers.

Clinically, the patient had early-onset Duchenne's muscular dystrophy. He walked without support at 27 months, but lost this ability at the age of 11 years. He had markedly elevated serum creatine kinase levels (range, 11,178 to 36,018 mU per milliliter; normal, 1 to 70); cardiomyopathy, which was diagnosed at the age of 12; mental retardation; and severe gastrointestinal disease, a rare complication of Duchenne's muscular dystrophy.5 He died at the age of 15 of acute intestinal occlusion and bleeding, respiratory failure, and cardiac arrhythmia. Two sisters were unaffected, but he was of gypsy ancestry; the family history was incomplete.

Western blotting and immunostaining were performed to see whether dystrophin and utrophin were present. Both were present in muscle-biopsy specimens from a normal control (Figure 1AFigure 1Immunohistochemical Analysis of Dystrophin (Left Side) and Utrophin (Right Side). and Figure 1B), and utrophin was present in a representative patient with Duchenne's muscular dystrophy (Figure 1C and Figure 1D). However, neither dystrophin nor utrophin could be detected in our patient (Figure 1E and Figure 1F), regardless of the antibody used (studies performed by L.V.B. Anderson, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom, and F. Pons, INSERM Unite 300, Montpellier, France). As observed in Duchenne's muscular dystrophy, immunostaining for the 50-kd dystrophin-associated glycoprotein was decreased (staining by F. Pons, data not shown). Ultrastructural studies showed that membrane integrity was preserved (studies by A.M. Pages). No deletion could be detected in the gene for Duchenne's muscular dystrophy by multiplex analysis with the polymerase chain reaction (data not shown).

It has been suggested that up-regulation of utrophin compensates for dystrophin deficiency,1,2,4 and in our patient disease progression was particularly severe. Dystrophin and utrophin are part of a complex of membrane proteins,1,3,4 abnormalities of which lead to several myopathies with closely related phenotypes.3 The absence of both proteins might arise from the absence of a common sarcolemmal protein, which would normally link them to the membrane. Our finding suggests that the expression of dystrophin, of utrophin, and of dystrophin-associated protein should all be systematically assessed in the diagnosis of muscular dystrophy, to establish whether sporadic or atypical forms of Duchenne's muscular dystrophy are caused by abnormalities of the dystrophin-glycoprotein complex or by utrophin deficiency.

Marie-Pierre Chevron, Ph.D.
INSERM Unite 249, 34033 Montpellier, France

Bernard Echenne, M.D.
Hopital Gui de Chauliac, 34000 Montpellier, France

Jacques Demaille, M.D., Ph.D.
INSERM Unite 249, 34033 Montpellier, France

5 References

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   Sewry CA, Sansome A, Matsumura K, Campbell KP, Dubowitz V. Deficiency of the 50 kDa dystrophin-associated glycoprotein and abnormal expression of utrophin in two south Asian cousins with variable expression of severe childhood autosomal recessive muscular dystrophy. Neuromuscul Disord 1994;4:121-129
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   Matsumura K, Ohlendieck K, Ionasescu VV, et al. The role of the dystrophin-glycoprotein complex in the molecular pathogenesis of muscular dystrophies. Neuromuscul Disord 1993;3:533-535
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   Matsumura K, Ervasti JM, Ohlendieck K, Kahl SD, Campbell KP. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Nature 1992;360:588-591
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   Barohn RJ, Levine EJ, Olson JO, Mendell JR. Gastric hypomotility in Duchenne's muscular dystrophy. N Engl J Med 1988;319:15-18
   Full Text | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   (1995) Dystrophin, Utrophin, and Muscular Dystrophy. New England Journal of Medicine 332:9, 612-613
   Full Text

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