Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Skin and Immune Diseases, Beijing, China.
Mckusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Clin Lab Anal. 2021 Jun;35(6):e23803. doi: 10.1002/jcla.23803. Epub 2021 May 24.
Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper- and hypo-pigmented macules on the face, trunk, and extremities. The condition causes severe cosmetic problem which can lead to significant psychological distress to the patients and bear a negative impact on society. DUH is a condition with genetic heterogeneity. The SASH1 gene was recently identified as pathogenic genes in DUH patients.
Two families clinically diagnosed with dyschromatosis universalis hereditaria were enrolled. Whole-exome sequencing combined with Sanger sequencing and bioinformatics analysis was performed in the probands. MutationTaster, CADD, SIFT, PolyPhen-2, and LRT software, and The American College of Medical Genetics and Genomics Standards and Guidelines were employed to assess the pathogenicity of detected missense mutations. One hundred healthy unrelated Chinese individuals were used as controls. All participants signed an informed consent form.
Genetic screening revealed a heterozygous SASH1 c.1547G>A (p.Ser516Asn) mutation for patients in family 1, and SASH1 c.1547G>T (p.Ser516Ile) for family 2. Both such de novo mutations are located in a highly conserved SLY domain in SASH1, have not been previously reported in any publication, and were not detected in any control databases.
The novel heterozygous mutations, SASH1 c.1547G>A and c.1547G>T, are likely responsible for the DUH phenotype in these two families. Our study expands the mutation spectrum of DUH. Whole-exome sequencing showed its efficiency in the diagnostic of hereditary skin disorders.
遗传性全身色素异常症（DUH）是一种罕见的遗传性皮肤病，其特征是面部、躯干和四肢出现色素沉着和色素减退斑。这种情况会导致严重的美容问题，给患者带来严重的心理困扰，并对社会产生负面影响。DUH 是一种具有遗传异质性的疾病。最近，SASH1 基因被确定为 DUH 患者的致病基因。
我们纳入了两个经临床诊断为遗传性全身色素异常症的家系。对先证者进行了全外显子组测序结合 Sanger 测序和生物信息学分析。采用 MutationTaster、CADD、SIFT、PolyPhen-2 和 LRT 软件以及美国医学遗传学与基因组学学院标准和指南评估了检测到的错义突变的致病性。100 名健康的无关中国个体作为对照。所有参与者均签署了知情同意书。
遗传筛查显示，家系 1 的患者存在 SASH1 基因 c.1547G>A（p.Ser516Asn）杂合突变，家系 2 的患者存在 SASH1 基因 c.1547G>T（p.Ser516Ile）杂合突变。这两种新的错义突变均位于 SASH1 的高度保守 SLY 结构域，以前未在任何出版物中报道过，也未在任何对照数据库中检测到。
这两种新的杂合突变，SASH1 c.1547G>A 和 c.1547G>T，可能是这两个家系 DUH 表型的原因。我们的研究扩展了 DUH 的突变谱。全外显子组测序显示其在遗传性皮肤疾病诊断中的效率。
