Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis

Patricia Y. Fechner, Sandra M. Marcantonio, Tsutomu Ogata, Ted O. Rosales, Kirby D. Smith, Peter N. Goodfellow, Claude J. Migeon, Gary Berkovitz

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The condition termed 46,XY complete gonadal dysgenesis is characterized by the lack of testicular determination with resulting streak gonads, normal Mullerian structures, and female external genitalia. In the partial form, there is incomplete testicular determination with a wide range in the degree of ambiguous genitalia and sexual duct development. We evaluated a kindred in which a partial form of 46,XY gonadal dysgenesis occurred in four subjects from two generations. Pedigree analysis indicated an X-linked or possibly an autosomal sex-limited mode of inheritance. All affected subjects were ascertained because of ambiguous genitalia with minimal virilization. At 10 days of age, the proband had a subnormal plasma level of testosterone, and at 4 months, there was no rise in plasma T after stimulation with hCG. At laparotomy, a dysgenetic gonad was found on the right side, but no gonad was found on the left side. A vas deferens was present on the right, indicating the presence of functional Leydig cells early in fetal life. In the other affected subjects, gonadal tissue was also limited to one side of the abdomen and showed poorly developed seminiferous tubules. The sex-determining region Y gene, which encodes the testig-determining factor, was present and unaltered in the genomic DNA of all affected subjects. Duplication of the distal short arm of the X-chromosome has been associated with 46,XY complete gonadal dysgenesis in some patients. In our studies, Southern blot analysis revealed that sequences of the distal short arm of the X-chromosome (DXS9 to DXS84) were present in single copy, excluding a large duplication in this area of the X. Several kindreds with familial 46,XY complete gonadal dysgenesis have been reported; five of them had evidence of an X-linked mode of inheritance. Our study of a kindred with 46,XY partial gonadal dyegenesis further supports the role of an X chromosome gene in testicular determination. Evidence of some fetal Leydig cell function in the affected subjects of our report suggests that mutations of the putative X-chromosome gene can result in a partial as well as complete defect in testicular determination.

Original languageEnglish
Pages (from-to)1248-1253
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume76
Issue number5
StatePublished - May 1 1993
Externally publishedYes

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46,XY Gonadal Dysgenesis
Chromosomes
X-Linked Genes
Gonads
Disorders of Sex Development
Leydig Cells
Genes
X Chromosome
sry Genes
Female Genitalia
Virilism
Plasmas
Sexual Development
Seminiferous Tubules
Vas Deferens
Pedigree
Southern Blotting
Abdomen
Ducts
Laparotomy

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Fechner, P. Y., Marcantonio, S. M., Ogata, T., Rosales, T. O., Smith, K. D., Goodfellow, P. N., ... Berkovitz, G. (1993). Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. Journal of Clinical Endocrinology and Metabolism, 76(5), 1248-1253.

Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. / Fechner, Patricia Y.; Marcantonio, Sandra M.; Ogata, Tsutomu; Rosales, Ted O.; Smith, Kirby D.; Goodfellow, Peter N.; Migeon, Claude J.; Berkovitz, Gary.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 76, No. 5, 01.05.1993, p. 1248-1253.

Research output: Contribution to journalArticle

Fechner, PY, Marcantonio, SM, Ogata, T, Rosales, TO, Smith, KD, Goodfellow, PN, Migeon, CJ & Berkovitz, G 1993, 'Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis', Journal of Clinical Endocrinology and Metabolism, vol. 76, no. 5, pp. 1248-1253.
Fechner PY, Marcantonio SM, Ogata T, Rosales TO, Smith KD, Goodfellow PN et al. Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. Journal of Clinical Endocrinology and Metabolism. 1993 May 1;76(5):1248-1253.
Fechner, Patricia Y. ; Marcantonio, Sandra M. ; Ogata, Tsutomu ; Rosales, Ted O. ; Smith, Kirby D. ; Goodfellow, Peter N. ; Migeon, Claude J. ; Berkovitz, Gary. / Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. In: Journal of Clinical Endocrinology and Metabolism. 1993 ; Vol. 76, No. 5. pp. 1248-1253.
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abstract = "The condition termed 46,XY complete gonadal dysgenesis is characterized by the lack of testicular determination with resulting streak gonads, normal Mullerian structures, and female external genitalia. In the partial form, there is incomplete testicular determination with a wide range in the degree of ambiguous genitalia and sexual duct development. We evaluated a kindred in which a partial form of 46,XY gonadal dysgenesis occurred in four subjects from two generations. Pedigree analysis indicated an X-linked or possibly an autosomal sex-limited mode of inheritance. All affected subjects were ascertained because of ambiguous genitalia with minimal virilization. At 10 days of age, the proband had a subnormal plasma level of testosterone, and at 4 months, there was no rise in plasma T after stimulation with hCG. At laparotomy, a dysgenetic gonad was found on the right side, but no gonad was found on the left side. A vas deferens was present on the right, indicating the presence of functional Leydig cells early in fetal life. In the other affected subjects, gonadal tissue was also limited to one side of the abdomen and showed poorly developed seminiferous tubules. The sex-determining region Y gene, which encodes the testig-determining factor, was present and unaltered in the genomic DNA of all affected subjects. Duplication of the distal short arm of the X-chromosome has been associated with 46,XY complete gonadal dysgenesis in some patients. In our studies, Southern blot analysis revealed that sequences of the distal short arm of the X-chromosome (DXS9 to DXS84) were present in single copy, excluding a large duplication in this area of the X. Several kindreds with familial 46,XY complete gonadal dysgenesis have been reported; five of them had evidence of an X-linked mode of inheritance. Our study of a kindred with 46,XY partial gonadal dyegenesis further supports the role of an X chromosome gene in testicular determination. Evidence of some fetal Leydig cell function in the affected subjects of our report suggests that mutations of the putative X-chromosome gene can result in a partial as well as complete defect in testicular determination.",
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AU - Rosales, Ted O.

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