PDF(Pubmed)
Abstract：
UNASSIGNED: Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that most often manifests hypogonadotropic hypogonadism (HH) and hypo-/anosmia due to early embryonic impairment in the migration of gonadotropin-releasing hormone neurons. SOX10 (SRY-Box 10; MIM*602229), a key transcriptional activator involved in the development of neural crest cells, has been associated with KS and is identified as one of the causative genes of Waardenburg syndrome (WS).
UNASSIGNED: A 28-year-old female patient, who was clinically diagnosed with KS in her childhood, presented with HH and anosmia, mild bilateral sensorineural hearing loss (SNHL), and pigmentation abnormalities. Next-generation sequencing analysis detected a missense heterozygous SOX10 pathogenic variant (NM_006941.4:c.506C>T) in the proposita and in her mother, whose phenotype included exclusively anosmia and hypopigmented skin patches. The same variant has been described by Pingault et al. [Clin Genet. 2015;88(4):352-9] in a patient with apparently isolated bilateral severe SNHL.
UNASSIGNED: Our finding substantiates the extreme phenotypic variability of SOX10-related disorders, which range from classical KS and/or WS to contracted endophenotypes that could share a common pathway in the development of neural crest cells and highlights the need for careful evaluation and long-term follow-up of SOX10 patients, with special focus on atypical/additional and/or late-onset phenotypic traits.
UNASSIGNED: A 28-year-old female patient, who was clinically diagnosed with KS in her childhood, presented with HH and anosmia, mild bilateral sensorineural hearing loss (SNHL), and pigmentation abnormalities. Next-generation sequencing analysis detected a missense heterozygous SOX10 pathogenic variant (NM_006941.4:c.506C>T) in the proposita and in her mother, whose phenotype included exclusively anosmia and hypopigmented skin patches. The same variant has been described by Pingault et al. [Clin Genet. 2015;88(4):352-9] in a patient with apparently isolated bilateral severe SNHL.
UNASSIGNED: Our finding substantiates the extreme phenotypic variability of SOX10-related disorders, which range from classical KS and/or WS to contracted endophenotypes that could share a common pathway in the development of neural crest cells and highlights the need for careful evaluation and long-term follow-up of SOX10 patients, with special focus on atypical/additional and/or late-onset phenotypic traits.
摘要：
■Kallmann综合征（KS）是一种遗传异质性发育障碍，由于促性腺激素释放激素神经元迁移的早期胚胎受损，通常表现为低促性腺激素性腺功能减退（HH）和低/缺失。SOX10(SRY-Box10;MIM*602229),参与神经c细胞发育的关键转录激活因子，已与KS相关，并被确定为Waardenburg综合征（WS）的致病基因之一。
■一位28岁的女性患者,她在童年时期被临床诊断出患有KS，表现为HH和嗅觉缺失，轻度双侧感音神经性听力损失（SNHL），和色素异常.下一代测序分析检测到一个错义杂合的SOX10致病变异体（NM_006941.4：c.506C>T），其表型仅包括嗅觉缺失和色素减退的皮肤斑块。Pingault等人已经描述了相同的变体。[ClinGenet。2015；88（4）：352-9]在明显孤立的双侧严重SNHL患者中。
■我们的发现证实了SOX10相关疾病的极端表型变异性，从经典的KS和/或WS到收缩的内表型，这些内表型可能在神经c细胞的发育中具有共同的途径，并强调需要对SOX10患者进行仔细评估和长期随访。特别关注非典型/额外和/或迟发性表型特征。
■一位28岁的女性患者,她在童年时期被临床诊断出患有KS，表现为HH和嗅觉缺失，轻度双侧感音神经性听力损失（SNHL），和色素异常.下一代测序分析检测到一个错义杂合的SOX10致病变异体（NM_006941.4：c.506C>T），其表型仅包括嗅觉缺失和色素减退的皮肤斑块。Pingault等人已经描述了相同的变体。[ClinGenet。2015；88（4）：352-9]在明显孤立的双侧严重SNHL患者中。
■我们的发现证实了SOX10相关疾病的极端表型变异性，从经典的KS和/或WS到收缩的内表型，这些内表型可能在神经c细胞的发育中具有共同的途径，并强调需要对SOX10患者进行仔细评估和长期随访。特别关注非典型/额外和/或迟发性表型特征。
