Zhang Yujing, Zhao Mengxi, Li Xiangqian, Zhao Yongping, Sun Yijie, Zhang Jianzhong, Yu Cong, Zhou Cheng
Department of Dermatology, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, China.
Department of Dermatology, Beijing Aerospace General Hospital, Beijing, China.
Hum Genomics. 2025 Jul 22;19(1):84. doi: 10.1186/s40246-025-00798-7.
Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome, and palmoplantar keratoderma. Currently, investigations into this disease are still limited, and its treatment remains elusive.
In this study, we aimed to report six Chinese patients who were diagnosed with hypotrichosis 14, whose conditions were attributed to five novel and recurrent variants in the LSS gene identified via whole exome sequencing. Moreover, the reported LSS gene has also been summarized.
We described six patients in five Chinese families with hair loss, and one of whom had a rare accompanying phenotype of hypergonadotropic hypogonadism, which has rarely been reported. Five novel variants were discovered in the LSS gene, including c.919_921del (p.His307del), c.1987 C > T (p.Arg663Trp), c.982 C > T (p.Arg328*), c.1405_1407del (p.Glu469del) and c.193_200dup (p.Pro68Argfs*14).
Our comprehensive summary of phenotypes caused by LSS gene variants not only enriches the existing knowledge on congenital hypotrichosis 14 but also provides crucial guidance for more accurate genetic counseling and potentially new directions for future research in understanding the disease mechanism and developing targeted therapies.
先天性少毛症14型是一种非综合征性脱发形式，与羊毛甾醇合酶（LSS）基因的致病变异相关。最近的研究扩展了LSS相关表型的范围，包括先天性白内障、脱发-智力障碍综合征和掌跖角化病。目前，对该疾病的研究仍然有限，其治疗方法仍不明确。
在本研究中，我们旨在报告6例被诊断为少毛症14型的中国患者，其病情归因于通过全外显子组测序鉴定出的LSS基因中的5种新的和复发性变异。此外，还对已报道的LSS基因进行了总结。
我们描述了来自5个中国家庭的6例脱发患者，其中1例伴有罕见的高促性腺激素性性腺功能减退表型，此前鲜有报道。在LSS基因中发现了5种新变异，包括c.919_921del（p.His307del）、c.1987 C>T（p.Arg663Trp）、c.982 C>T（p.Arg328*）、c.1405_1407del（p.Glu469del）和c.193_200dup（p.Pro68Argfs*14）。
我们对LSS基因变异引起的表型进行的全面总结不仅丰富了现有的先天性少毛症14型知识，而且为更准确的遗传咨询提供了关键指导，并为未来理解疾病机制和开发靶向治疗的研究提供了潜在的新方向。
