Frolova E B, Petrov V M, Vasilyev E V, Makretskaya N A, Pilipenko O V, Tyulpakov A N
National Medical Research Center of Children Health.
Endocrinology Research Centre.
Probl Endokrinol (Mosk). 2021 Sep 7;67(5):43-47. doi: 10.14341/probl12789.
More than 30 genes are known to take part in hypothalamic-pituitary-gonadal axis development at the date and role of more than 10 other genes is studied. Despite it about 50% of isolated hypogonadotropic hypogonadism cases still have no molecular genetic explanation.A number of specific associations between iHH and different not-reproductive manifestations called syndromic forms are distinguished in general group of iHH. For example, the combination of Kalmann syndrome with sensorineural hearing loss is known as manifestation for defects of some genes encoding factors of neuronal migration; in patients with this phenotype CHD7, SOX10 genes defects are most frequent. However, defects in the genes of neuronal migration factors are characterized by a wide variability of phenotype, which is explained by the epigenetic mechanisms influence. Carriers of the mutation within the same family may lack some non-reproductive manifestations as well as hypogonadism.Here we present a case of Kalmann syndrome in monozygous twins, caused by a previously not described heterozygous mutation c.462C> G: p.I154M in the SOX10 gene in the absence of sensorineural hearing loss. The mutation was inherited from a father who has only isolated anosmia in the phenotype. This mutation was identified during full exome sequencing. This unique observation for Russia shows on the one hand expediency to check SOX10 sequence in addition to the other factors of neuronal migration and differentiation and, on the other hand, the prospect of full exome sequencing in a group of patients with undifferentiated iHH.
目前已知有30多个基因参与下丘脑 - 垂体 - 性腺轴的发育，还有10多个基因的作用正在研究中。尽管如此，约50%的孤立性低促性腺激素性性腺功能减退病例仍无法得到分子遗传学解释。在孤立性低促性腺激素性性腺功能减退的总体病例中，可区分出一些与不同非生殖表现相关的特定关联，即综合征形式。例如，卡尔曼综合征与感音神经性听力损失的组合被认为是某些编码神经元迁移因子的基因缺陷的表现；具有这种表型的患者中，CHD7、SOX10基因缺陷最为常见。然而，神经元迁移因子基因的缺陷表现出广泛的表型变异性，这是由表观遗传机制的影响所致。同一家族中的突变携带者可能既没有某些非生殖表现，也没有性腺功能减退。在此，我们报告一例单卵双胞胎中的卡尔曼综合征病例，其由SOX10基因中一个先前未描述的杂合突变c.462C>G:p.I154M引起，且不存在感音神经性听力损失。该突变遗传自表型仅为孤立性嗅觉缺失的父亲。此突变是在全外显子测序过程中发现的。这一在俄罗斯的独特观察结果一方面表明，除了检查其他神经元迁移和分化因子外，检查SOX10序列是有必要的；另一方面也显示了在一组未分化的孤立性低促性腺激素性性腺功能减退患者中进行全外显子测序的前景。
