Whole-exome sequencing enables rapid and prenatal diagnosis of inherited skin disorders

BMC Medical Genomics

Research

Luo Na¹  Zhang Kexin¹  Wang Ziyi²  Wang Junwen²  Zhu Xintong²  Guo Hong² 

[1] Department of Dermatology, Southwest Hospital, Army Medical University, 30# Gaotanyan St., Shapingba District, 400038, Chongqing, P.R. China;Department of Medical Genetics, College of Basic Medical Science, Army Medical University, 30# Gaotanyan St., Shapingba District, 400038, Chongqing, P.R. China;

关键词: Inherited skin disorders;    Genetic diagnosis;    Prenatal diagnosis;    Whole exome sequencing (WES);    Genetic counseling;   

DOI  :  10.1186/s12920-023-01628-2

 received in 2022-08-21, accepted in 2023-08-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGenodermatoses are a broad group of disorders with specific or non-specific skin-based phenotypes, most of which are monogenic disorders. However, it’s a great challenge to make a precise molecular diagnosis because of the clinical heterogeneity. The genetic and clinical heterogeneity brings great challenges for diagnosis in dermatology. The whole exome sequencing (WES) not only expedites the discovery of the genetic variations, but also contributes to genetic counselling and prenatal diagnosis.Materials and methodsFollowed by the initial clinical and pathological diagnosis, genetic variations were identified by WES. The pathogenicity of the copy number variations (CNVs) and single-nucleotide variants (SNVs) were evaluated according to ACMG guidelines. Candidate pathogenic SNVs were confirmed by Sanger sequencing in the proband and the family members.ResultsTotally 25 cases were recruited. Nine novel variations, including c.5546G > C and c.1457delC in NF1, c.6110G > T in COL7A1, c.2127delG in TSC1, c.1445 C > A and c.1265G > A in TYR, Xp22.31 deletion in STS, c.908 C > T in ATP2A2, c.1371insC in IKBKG, and nine known ones were identified in 16 cases (64%). Prenatal diagnosis was applied in 6 pregnant women by amniocentesis, two of whom carried positive findings.ConclusionsOur findings highlighted the value of WES as a first-tier genetic test in determining the molecular diagnosis. We also discovered the distribution of genodermatoses in this district, which provided a novel clinical dataset for dermatologists.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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