Calvel Pierre, Kusz-Zamelczyk Kamila, Makrythanasis Periklis, Janecki Damian, Borel Christelle, Conne Béatrice, Vannier Anne, Béna Frédérique, Gimelli Stefania, Fichna Piotr, Antonarakis Stylianos E, Nef Serge, Jaruzelska Jadwiga
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Sex Dev. 2015;9(5):289-95. doi: 10.1159/000441512. Epub 2015 Nov 7.
We report the case of a female patient suffering from a 46,XY disorder of sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence of these 2 conditions has not yet been reported. Using whole exome sequencing and comparative genome hybridization array, we identified a de novo MLL/KMT2A gene nonsense mutation which explains the WDSTS phenotype. In addition, we discovered novel genetic variants, which could explain the testicular dysgenesis observed in the patient, a maternally inherited 167-kb duplication of DAAM2 and MOCS1 genes and a de novo LRRC33/NRROS gene mutation. These genes, some of which are expressed during mouse gonadal development, could be considered as potentially new candidate genes for DSD.
我们报告了一例患有46,XY性发育障碍（DSD）且伴有完全性腺发育不全和维德曼-施泰纳综合征（WDSTS）的女性患者。这两种病症并存的情况尚未见报道。通过全外显子组测序和比较基因组杂交阵列，我们鉴定出一个从头发生的MLL/KMT2A基因无义突变，该突变解释了WDSTS的表型。此外，我们还发现了新的基因变异，这些变异可以解释在该患者中观察到的睾丸发育不全，即母系遗传的DAAM2和MOCS1基因167 kb重复以及一个从头发生的LRRC33/NRROS基因突变。其中一些基因在小鼠性腺发育过程中表达，可被视为DSD潜在的新候选基因。
