Department of Dermatology and Cutaneous Biology and.
Jefferson Institute of Molecular Medicine, Sidney Kimmel Medical College, and.
JCI Insight. 2022 Apr 22;7(8):e156021. doi: 10.1172/jci.insight.156021.
Severe viral infections of the skin can occur in patients with inborn errors of immunity (IEI). We report an all-in-one whole-transcriptome sequencing-based method by RNA-Seq on a single skin biopsy for concomitantly identifying the cutaneous virome and the underlying IEI. Skin biopsies were obtained from healthy and lesional skin from patients with cutaneous infections suspected to be of viral origin. RNA-Seq was utilized as the first-tier strategy for unbiased human genome-wide rare variant detection. Reads unaligned to the human genome were utilized for the exploration of 926 viruses in a viral genome catalog. In 9 families studied, the patients carried pathogenic variants in 6 human IEI genes, including IL2RG, WAS, CIB1, STK4, GATA2, and DOCK8. Gene expression profiling also confirmed pathogenicity of the human variants and permitted genome-wide homozygosity mapping, which assisted in identification of candidate genes in consanguineous families. This automated, online, all-in-one computational pipeline, called VirPy, enables simultaneous detection of the viral triggers and the human genetic variants underlying skin lesions in patients with suspected IEI and viral dermatosis.
严重的皮肤病毒感染可能发生在先天性免疫缺陷（IEI）患者中。我们报告了一种基于 RNA-Seq 的整体转录组测序方法，通过单次皮肤活检同时鉴定皮肤病毒组和潜在的 IEI。从疑似病毒感染的健康和病变皮肤中获取皮肤活检。RNA-Seq 被用作无偏人类全基因组稀有变异检测的一线策略。未与人类基因组对齐的读取用于探索病毒基因组目录中的 926 种病毒。在研究的 9 个家族中，患者携带 6 个人类 IEI 基因的致病性变异，包括 IL2RG、WAS、CIB1、STK4、GATA2 和 DOCK8。基因表达谱分析也证实了人类变异的致病性，并允许进行全基因组纯合性映射，这有助于在同系家族中鉴定候选基因。这种自动化、在线、一体化的计算管道称为 VirPy，能够同时检测疑似 IEI 和病毒性皮肤病患者皮肤损伤中的病毒触发因素和人类遗传变异。
