Lipoid Proteinosis Due to Homozygous Nonsense Mutation in Extracellular Matrix Protein 1 (ECM1) Gene in Three Pakistani Siblings

Abstract

Introduction Urbach–Wiethe disease (or lipoid proteinosis) is an autosomal recessive genetic disease. It is caused by a mutation in the extracellular matrix protein 1 gene (ECM1), resulting in deposition of hyaline material at the dermoepidermal junction of the skin, around blood vessels, and at multiple other sites. Case presentation The present report describes three siblings born to nonconsanguineous parents who presented with hoarseness, macroglossia, yellow waxy skin, beaded papules on the eyelids, atrophic scars, and recurrent skin infections. Histopathologic examination showed hyaline deposition at the interface between the dermis and epidermis and at the basal lamina of blood vessels. Exome sequencing revealed a homozygous nonsense variant in ECM1. This variant created a premature stop codon, leading to loss of function. Both parents were heterozygous for the same mutation. Conclusion This report is a useful addition to the current knowledge base regarding this phenotypically and genetically variable genodermatosis, which is rarely reported in Pakistan.