<p>From Clinical Phenotype to Genotypic Modelling: Incidence and Prevalence of Recessive Dystrophic Epidermolysis Bullosa (RDEB)</p>

作者：Shaundra Eichstadt, Jean Y. Tang, D. Solis, Zurab Siprashvili, M. Peter Marinkovich, Nedra Whitehead, Matthew Schu, Fang Fang, Stephen W. Erickson, Mary E. Ritchey, Max Colao, Kaye Spratt, Amir Shaygan, Mark J. Ahn, Kavita Y. Sarin · 发表于：Clinical Cosmetic and Investigational Dermatology · 年份：2019 · DOI：10.2147/ccid.s232547 · 被引用次数：34 · 研究领域：Skin and Cellular Biology Research、Genetic and rare skin diseases.、Cellular transport and secretion

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited genetic disorder characterized by recurrent and chronic open wounds with significant morbidity, impaired quality of life, and early mortality. RDEB patients demonstrate reduction or structural alteration type VII collagen (C7) owing to mutations in the gene COL7A1 , the main component of anchoring fibrils (AF) necessary to maintain epidermal-dermal cohesion. While over 700 alterations in COL7A1 have been reported to cause dystrophic epidermolysis bullosa (DEB), which may be inherited in an autosomal dominant (DDEB) or autosomal recessive pattern (RDEB), the incidence and prevalence of RDEB is not well defined. To date, the widely estimated incidence (0.2– 6.65 per million births) and prevalence (3.5– 20.4 per million people) of RDEB has been primarily characterized by limited analyses of clinical databases or registries. Methods: Using a genetic modelling approach, we use whole exome and genome sequencing data to estimate the allele frequency of pathogenic variants. Through the ClinVar and NCBI database of human genome variants and phenotypes, DEB Register, and analyzing premature COL7A1 termination variants we built a model to predict the pathogenicity of previously unclassified variants. We applied the model to publicly available sequences from the Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) and identified variants which were classified as pathogenic for RDEB from ...