Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
Medicine (Baltimore). 2023 Aug 4;102(31):e34448. doi: 10.1097/MD.0000000000034448.
Dyschromatosis universalis hereditaria (DUH) is an uncommon form of pigmented genodermatosis that is typically inherited autosomally and dominantly. In the previous study, the pathogenic genes of DUH have been identified in ATP-binding cassette subfamily B, member 6 and SASH1. However, the mutational screening of the causative gene remains incomplete and still lacks sufficient proof in the etiology.
A 2-generation Chinese family clinically diagnosed with DUH were enrolled. They showed pigmented spots from their childhood and came to the hospital for medical advice and genetic analysis. We found a novel mutation c.1757T > C (p.I586T) of SASH1 in 3 affected family members by whole-exome sequencing.
Genetic outcomes and clinical examinations confirmed the diagnosis of DUH in 3 family members with lentiginous syndrome.
Using whole-exome sequencing and sanger sequencing technologies, we identified a novel mutation c.1757T > C (p.I586T) of SASH1 that co-segregated in 3 afflicted family members but not in the normal individuals. Significantly, c.1757T > C (p.I586T) is a novel mutation which had not been previously reported. The same codon position in SASH1 (c.1758C > G, p.I586M) has been reported in a Japanese man, and he showed identical phenotype compared to our study participants.
Our study broadens the spectrum of DUH mutations and provides more genetic characteristics of DUH in understanding its etiology. Furthermore, we demonstrated the diagnostic accuracy of whole-exome sequencing for inherited skin diseases and provided new information for etiological study.
遗传型全身性色素异常（DUH）是一种罕见的色素性遗传性皮肤病，通常为常染色体显性遗传。在之前的研究中，已经确定了 DUH 的致病基因是 ATP 结合盒亚家族 B，成员 6 和 SASH1。然而，导致疾病的基因突变的筛查仍然不完整，在病因学方面仍然缺乏足够的证据。
一个 2 代中国家族患有 DUH，他们从儿童时期就出现色素斑，并前来医院就诊和进行基因分析。我们通过全外显子组测序发现了 3 个受影响的家族成员中的一个新突变 c.1757T > C（p.I586T）。
通过基因检测和临床检查，我们确认了这 3 名患者的 DUH 诊断，他们均患有雀斑样痣综合征。
我们使用全外显子组测序和 Sanger 测序技术，发现了 SASH1 中的一个新突变 c.1757T > C（p.I586T），该突变在 3 名受累家族成员中共同遗传，但在正常个体中不存在。值得注意的是，c.1757T > C（p.I586T）是一个新的突变，之前没有报道过。SASH1 中相同的密码子位置（c.1758C > G，p.I586M）已经在一名日本男性中报道过，他与我们的研究参与者表现出相同的表型。
我们的研究拓宽了 DUH 突变谱，并提供了更多关于 DUH 病因的遗传特征。此外，我们证明了全外显子组测序在遗传性皮肤病诊断中的准确性，并为病因学研究提供了新的信息。
