Bhagavath Bala, Layman Lawrence C, Ullmann Reinhard, Shen Yiping, Ha Kyungsoo, Rehman Khurram, Looney Stephen, McDonough Paul G, Kim Hyung-Goo, Carr Bruce R
Division of Reproductive Endocrinology and Infertility, Department of OB/GYN, University of Rochester Medical Center, Rochester, NY 14642, United States.
Section of Reproductive Endocrinology, Infertility and Genetics, Department of OB/GYN, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, United States.
Mol Cell Endocrinol. 2014 Aug 5;393(1-2):1-7. doi: 10.1016/j.mce.2014.05.006. Epub 2014 Jun 4.
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.
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.
A 349kb heterozygous deletion located 353kb 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.
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.
46,XY性反转是一种罕见的疾病，家族性病例更为罕见。本研究的目的是确定一个有三名患46,XY性反转的患病兄弟姐妹的家庭的分子基础。
从三名患有46,XY性反转的女性、两名正常姐妹以及父母双方提取DNA。对SRY和NR5A1基因的所有蛋白质编码外显子进行基于PCR的DNA测序。此外，对所有七名家庭成员的DNA进行阵列比较基因组杂交。使用定量聚合酶链反应确认缺失。使用逆转录聚合酶链反应定量SOX9基因的表达。
在父亲和三名患病兄弟姐妹中发现了位于17号染色体长臂上SOX9基因上游353kb处的一个349kb杂合缺失，但母亲中未发现。患病兄弟姐妹中SOX9的表达显著降低。三名患病姐妹中有两名患有性腺母细胞瘤。
这是首次报道三名兄弟姐妹发生46,XY性反转，其父亲遗传了SOX9上游的缺失，且与SOX9 mRNA表达降低有关。
