46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism
46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism
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DOI：
10.1111/j.1399-0004.2011.01832.x
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发表时间：
2012-12-01
影响因子：
3.5
通讯作者：
Deal, C. L.
中科院分区：
文献类型：
--
作者：
Stoppa-Vaucher, S.;Ayabe, T.;Deal, C. L.
对于新生突变的家族复发风险知之甚少。如果发生父母种系嵌合体，复发风险可能比通常认为的要高，这对遗传咨询和临床实践具有影响。在治疗患有青春期延迟和高促性腺激素性性腺功能减退症的女性的过程中，我们在 SRY 基因中发现了一个新的错义突变，导致这个核型正常的 XY 个体的体细胞女性化。尽管青春期正常开始，我们还是测试了一位妹妹，她也具有 XY 核型和相同的 SRY 突变。姐姐的影像学检查显示她患有卵巢肿瘤，已被切除。父亲血液中的 DNA 具有野生型 SRY 序列，亲子鉴定与给定的家庭结构一致。一个兄弟年龄 46，XY，具有野生型 SRY 序列，强烈表明该突变存在父系 Y 染色体种系嵌合现象。对于性发育障碍（DSD），早期诊断对于受影响患者的最佳心理发育至关重要。在这种情况下，预防性核型筛查可以在正常青春期年龄之前早期诊断兄弟姐妹的性腺肿瘤。我们的结果表明，细胞学或分子诊断应该适用于受影响的 DSD 个体的兄弟姐妹。
Familial recurrence risks are poorly understood in cases of de novo mutations. In the event of parental germ line mosaicism, recurrence risks can be higher than generally appreciated, with implications for genetic counseling and clinical practice. In the course of treating a female with pubertal delay and hypergonadotropic hypogonadism, we identified a new missense mutation in the SRY gene, leading to somatic feminization of this karyotypically normal XY individual. We tested a younger sister despite a normal onset of puberty, who also possessed an XY karyotype and the same SRY mutation. Imaging studies in the sister revealed an ovarian tumor, which was removed. DNA from the father's blood possessed the wild type SRY sequence, and paternity testing was consistent with the given family structure. A brother was 46, XY with a wild type SRY sequence strongly suggesting paternal Y-chromosome germline mosaicism for the mutation. In disorders of sexual development (DSDs), early diagnosis is critical for optimal psychological development of the affected patients. In this case, preventive karyotypic screening allowed early diagnosis of a gonadal tumor in the sibling prior to the age of normal puberty. Our results suggest that cytological or molecular diagnosis should be applied for siblings of an affected DSD individual.