A novel SOX10 nonsense mutation in a patient with Kallmann syndrome and Waardenburg syndrome
A novel SOX10 nonsense mutation in a patient with Kallmann syndrome and Waardenburg syndrome
复制标题
DOI：
10.1530/edm-20-0145
复制
发表时间：
2021-04-27
影响因子：
0.9
通讯作者：
Ishibashi, Shun
中科院分区：
文献类型：
--
作者：
Wakabayashi, Tetsuji;Takei, Akihito;Ishibashi, Shun
卡尔曼综合征是一种罕见的遗传性疾病，其特征是由于胚胎发育过程中嗅神经轴突发育受损以及促性腺激素释放激素（GNRH）产生神经元迁移异常，导致嗅觉缺失和低促性腺激素性性腺功能减退。其潜在的遗传驱动因素在很大程度上仍然未知。SOX10是一种参与神经嵴细胞发育的关键转录因子，已被确定为瓦尔登堡综合征的致病基因之一，也已被证明是卡尔曼综合征的致病基因。一名17岁男性患者，童年时因听力障碍和虹膜色素减退被诊断为瓦尔登堡综合征，因嗅觉缺失和青春期发育延迟转诊至我科。由于临床检查显示嗅球发育不全和低促性腺激素性性腺功能减退，我们诊断他患有卡尔曼综合征。偶然地，我们发现他还伴有亚临床甲状腺功能减退，但没有自身免疫性甲状腺炎的证据。直接测序分析在该患者中检测到一个无义SOX10突变（c.373C>T，p.Glu125X）。由于该无义突变从未作为种系变异被报道过，所以这个SOX10替代是一种导致卡尔曼综合征和瓦尔登堡综合征的新型突变。该病例证实了SOX10作为卡尔曼综合征和瓦尔登堡综合征遗传病因的重要性，这两种疾病可能在神经嵴细胞发育过程中共享一个共同的途径。
The underlying genetic drivers of Kallmann syndrome, a rare genetic disorder characterized by anosmia and hypogonadotropic hypogonadism due to impairment in the development of olfactory axons and in the migration of gonadotropin-releasing hormone (GNRH)-producing neurons during embryonic development, remain largely unknown. SOX10, a key transcription factor involved in the development of neural crest cells and established as one of the causative genes of Waardenburg syndrome, has been shown to be a causative gene of Kallmann syndrome. A 17-year-old male patient, who was diagnosed with Waardenburg syndrome on the basis of a hearing impairment and hypopigmented iris at childhood, was referred to our department because of anosmia and delayed puberty. As clinical examination revealed an aplastic olfactory bulb and hypogonadotropic hypogonadism, we diagnosed him as having Kallmann syndrome. Incidentally, we elucidated that he also presented with subclinical hypothyroidism without evidence of autoimmune thyroiditis. Direct sequence analysis detected a nonsense SOX10 mutation (c.373C>T, p.Glu125X) in this patient. Since this nonsense mutation has never been published as a germline variant, the SOX10 substitution is a novel mutation that results in Kallmann syndrome and Waardenburg syndrome. This case substantiates the significance of SOX10 as a genetic cause of Kallmann syndrome and Waardenburg syndrome, which possibly share a common pathway in the development of neural crest cells.