Szczerbal Izabela, Nowacka-Woszuk Joanna, Dzimira Stanislaw, Atamaniuk Wojciech, Nizanski Wojciech, Switonski Marek
Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
Sex Dev. 2016;10(2):74-8. doi: 10.1159/000445464. Epub 2016 Apr 19.
Testicular or ovotesticular disorder of sex development (DSD) in genetic females (78,XX; SRY-negative) has been reported quite frequently in numerous dog breeds and is usually diagnosed due to the presence of female external genitalia with an enlarged clitoris. The molecular background of this disorder, diagnosed also in human and other mammals, is not fully understood. However, it has recently been proposed that a copy number variation (CNV) in the region upstream of the SOX9 gene is associated with it. We described a rare case of this disorder in a French Bulldog with abdominal testes and male external genitalia (a slightly malformed penis). FISH studies showed a female karyotype, lack of a translocation involving the Y chromosome, and a distinct size variation in the CNV region (CNVR) upstream of the SOX9 gene, located on chromosome 9 (CFA9). A large FISH variant on a single CFA9 and a lack of the variant on its homologue was observed. Surprisingly, in the mother of this DSD dog, 2 normal-sized variants were identified which means that the CNV in the DSD dog was de novo. Our observations are in agreement with earlier suggestions that a high number of copies at the CNVR upstream of SOX9 may be associated with this type of DSD.
在遗传雌性犬（78,XX；SRY阴性）中，睾丸或卵睾性发育障碍（DSD）在众多犬种中屡有报道，通常因雌性外生殖器伴有增大的阴蒂而被诊断出来。这种在人类和其他哺乳动物中也有诊断出的疾病的分子背景尚未完全明确。然而，最近有人提出，SOX9基因上游区域的拷贝数变异（CNV）与之相关。我们描述了一例法国斗牛犬的这种罕见疾病病例，该犬具有腹腔睾丸和雄性外生殖器（阴茎稍有畸形）。荧光原位杂交（FISH）研究显示其核型为雌性，不存在涉及Y染色体的易位，且位于9号染色体（CFA9）上的SOX9基因上游拷贝数变异区域（CNVR）有明显的大小差异。观察到单个CFA9上有一个大的FISH变异，而其同源染色体上没有该变异。令人惊讶的是，在这只患有DSD的犬的母亲中，鉴定出了两个正常大小的变异，这意味着该DSD犬的CNV是新生的。我们的观察结果与早期的观点一致，即SOX9上游CNVR处的高拷贝数可能与这种类型的DSD有关。
