Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene

Bala Bhagavath, Lawrence C. Layman, Reinhard Ullmann, Yiping Shen, Kyungsoo Ha, Khurram Rehman, Stephen Looney, Paul G. McDonough, Hyung Goo Kim, Bruce R. Carr

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: 46,XY sex reversal is a rare disorder and familial cases are even more rare. The purpose of the present study was to determine the molecular basis for a family with three affected siblings who had 46,XY sex reversal. Methods: DNA was extracted from three females with 46,XY sex reversal, two normal sisters, and both unaffected parents. All protein coding exons of the SRY and NR5A1 genes were subjected to PCR-based DNA sequencing. In addition, array comparative genomic hybridization was performed on DNA from all seven family members. A deletion was confirmed using quantitative polymerase chain reaction. Expression of SOX9 gene was quantified using reverse transcriptase polymerase chain reaction. Results: A 349. kb heterozygous deletion located 353. kb upstream of the SOX9 gene on the long arm of chromosome 17 was discovered in the father and three affected siblings, but not in the mother. The expression of SOX9 was significantly decreased in the affected siblings. Two of three affected sisters had gonadoblastomas. Conclusion: This is the first report of 46,XY sex reversal in three siblings who have a paternally inherited deletion upstream of SOX9 associated with reduced SOX9 mRNA expression.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume393
Issue number1-2
DOIs
StatePublished - Aug 5 2014

Fingerprint

Campomelic Dysplasia
Siblings
Genes
Polymerase chain reaction
DNA
RNA-Directed DNA Polymerase
Chromosomes
Exons
Gonadoblastoma
Polymerase Chain Reaction
Messenger RNA
Chromosomes, Human, Pair 17
Comparative Genomic Hybridization
Reverse Transcriptase Polymerase Chain Reaction
DNA Sequence Analysis
Fathers
Proteins
Parents
Mothers
Gene Expression

Keywords

  • Gonadal dysgenesis
  • NR5A1
  • SOX9
  • SRY
  • XY sex reversal

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene. / Bhagavath, Bala; Layman, Lawrence C.; Ullmann, Reinhard; Shen, Yiping; Ha, Kyungsoo; Rehman, Khurram; Looney, Stephen; McDonough, Paul G.; Kim, Hyung Goo; Carr, Bruce R.

In: Molecular and Cellular Endocrinology, Vol. 393, No. 1-2, 05.08.2014, p. 1-7.

Research output: Contribution to journalArticle

Bhagavath, B, Layman, LC, Ullmann, R, Shen, Y, Ha, K, Rehman, K, Looney, S, McDonough, PG, Kim, HG & Carr, BR 2014, 'Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene', Molecular and Cellular Endocrinology, vol. 393, no. 1-2, pp. 1-7. https://doi.org/10.1016/j.mce.2014.05.006
Bhagavath, Bala ; Layman, Lawrence C. ; Ullmann, Reinhard ; Shen, Yiping ; Ha, Kyungsoo ; Rehman, Khurram ; Looney, Stephen ; McDonough, Paul G. ; Kim, Hyung Goo ; Carr, Bruce R. / Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene. In: Molecular and Cellular Endocrinology. 2014 ; Vol. 393, No. 1-2. pp. 1-7.
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AU - Ha, Kyungsoo

AU - Rehman, Khurram

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