Correspondence

Detection of Y-Chromosome Sequences in Gonadal Tissue of Patients with Turner's Syndrome (45,X)

N Engl J Med 1994; 331:682-683September 8, 1994

Article

To the Editor:

Molecular biologic techniques for the detection of Y-chromosome sequences have illustrated the limitations of cytogenetic analysis in the evaluation of patients with Turner's syndrome1,2. In previous studies using Southern blot analysis of DNA amplified by the polymerase chain reaction, we found the SRY gene in 30 percent of patients in whom a Y chromosome was not detected in peripheral-blood lymphocytes or skin fibroblasts3. Although gonadal tumors are uncommon in patients with Turner's syndrome, detection of Y-chromosome DNA sequences is important because of the increased likelihood of gonadal tumors in dysgenetic gonads containing such sequences.

With the use of specific primers and probes, the presence of different segments of Y-chromosome DNA can be detected by Southern blot analysis of amplified DNA in a sensitive and specific fashion3,4. Fluorescence in situ hybridization can be used to confirm the presence and location of Y-chromosome sequences within tissue sections or on chromosome spreads. With the concurrent use of Southern blot amplification with six Y-chromosome-specific probes (PABY, SRY, ZFY, DYZ3, KAL-Y, and DYZ1) and fluorescence in situ hybridization with a probe that combines DNA segments specific for the DYZ1 and DYZ3 loci, we have demonstrated the presence of Y-chromosome DNA sequences in paraffin-embedded gonadal tissue from three patients with Turner's syndrome (Figure 1Figure 1Photomicrograph of Gonadal Tissue, Highlighting a Group of Intratubular Cells with Positive Yellow-Green Intranuclear Signals (Arrowheads) Indicating the Centromere Sequence and Repetitive Sequences of the Long Arm of the Y Chromosome.). (The tissue was kindly provided by Drs. Margaret H. MacGillivray, John E. Fisher, Edward O. Reiter, Peter A. Lee, and Paul S. Dickman.) All three patients had atypical features, including gonadoblastoma, clitoromegaly, and genital ambiguity5.

These results support the concept that Turner's syndrome and mixed gonadal dysgenesis may compose a spectrum extending from 45,X monosomy with absent or undetectable Y-chromosome DNA and bilateral streak gonads to a 45,X/46,XY karyotype with a male phenotype and dysgenetic testes. The risk of gonadal tumors, extent of virilization, and degree of male differentiation may depend both on the proportion of Y-chromosome-bearing cells and on the specific segment of the Y chromosome that is present. Prospective evaluation of many patients will be needed to assess the actual risk of virilization and neoplastic transformation resulting from micromosaicism for Y-chromosome material.

Mirjana Kocova, M.D., Ph.D.
Selma F. Siegel, M.D.
Michael Nalesnick, M.D.
Massimo Trucco, M.D.
University of Pittsburgh, Pittsburgh, PA 15213

5 References

1. 1

   Muller U, Donlon TA, Kunkel SM, Lalande M, Latt SA. Y-190, a DNA probe for the sensitive detection of Y-derived marker chromosomes and mosaicism. Hum Genet 1987;75:109-113
   CrossRef | Web of Science | Medline

2. 2

   Nagafuchi S, Tamura T, Nakahori Y, et al. The majority of the marker chromosomes in Japanese patients with stigmata of Turner syndrome are derived from Y chromosomes. Hum Genet 1992;89:590-592
   CrossRef | Web of Science | Medline

3. 3

   Kocova M, Siegel SF, Wenger SL, Lee PA, Trucco M. Detection of Y chromosome sequences in Turner's syndrome by Southern blot analysis of amplified DNA. Lancet 1993;342:140-143
   CrossRef | Web of Science | Medline

4. 4

   Vollrath D, Foote S, Hilton A, et al. The human Y chromosome: a 43-interval map based on naturally occurring deletions. Science 1992;258:52-59
   CrossRef | Web of Science | Medline

5. 5

   Lindsay AN, Sills IN, MacGillivray MH, Fisher JE, Voorhess ML. Dysgerminoma in a patient with the syndrome of gonadal dysgenesis with a 45,X karyotype. Am J Med Genet 1981;10:21-24
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Mirjana Kocova, Selma Feldman Witchel, Michael Nalesnik, Peter A. Lee, Paul S. Dickman, Margaret H. MacGillivray, Edward O. Reiter, Giuliana Trucco, Massimo Trucco. (1995) Y chromosomal sequences identified in gonadal tissue of two 45,X patients with turner syndrome. Endocrine Pathology 6:4, 311-322
   CrossRef