Mazen Inas, Abdel-Hamid Mohamed, Mekkawy Mona, Bignon-Topalovic Joëlle, Boudjenah Radia, El Gammal Mona, Essawi Mona, Bashamboo Anu, McElreavey Ken
Department of Clinical Genetics, National Research Center, Cairo, Egypt.
Sex Dev. 2016;10(3):147-51. doi: 10.1159/000445983. Epub 2016 May 12.
The phenotypic spectrum of patients carrying NR5A1 mutations ranges from 46,XY gonadal dysgenesis to male infertility. Phenotypic variability could be due to digenic or oligogenic inheritance of pathogenic variants in other testis-determining genes. Here, exome sequencing identified 2 pathogenic de novo NR5A1 mutations in 2 patients with 46,XY gonadal dysgenesis, p.Q206Tfs*20 and p.Arg313Cys. The latter patient also carried a missense mutation in MAP3K1. Our data extend the number of NR5A1 gene mutations associated with gonadal dysgenesis. The combination of an NR5A1 mutation with a MAP3K1 variant may explain the phenotypic variability associated with NR5A1 mutations.
携带NR5A1突变的患者的表型谱范围从46,XY性腺发育不全到男性不育。表型变异性可能归因于其他睾丸决定基因中致病变异的双基因或寡基因遗传。在此，外显子组测序在2例46,XY性腺发育不全患者中鉴定出2种致病性新发NR5A1突变，即p.Q206Tfs*20和p.Arg313Cys。后一名患者在MAP3K1中还携带一个错义突变。我们的数据扩展了与性腺发育不全相关的NR5A1基因突变的数量。NR5A1突变与MAP3K1变异的组合可能解释了与NR5A1突变相关的表型变异性。
