Short Case ReportsWhole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosaRehman, Atta Ura; Peter, Virginie G.a; Quinodoz, Mathieua; Dawood, Muhammadb; Rivolta, Carloa,,c,,d,,eAuthor Information aDepartment of Computational Biology, Unit of Medical Genetics, University of Lausanne, Switzerland bDepartment of Dermatology, District Headquarter Hospital Khar, District Bajaur, Khyber Pakhtunkhwa, Pakistan cDepartment of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom dClinical Research Center, Institute of Molecular and Clinical Ophthalmology Basel (IOB) eDepartment of Ophthalmology, University Hospital Basel, Basel, Switzerland Received 13 May 2019 Accepted 19 August 2019 Correspondence to Atta Ur Rehman, Mphil, Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne, Switzerland, Tel: +41 21 692 5469; fax: +41 21 692 5455; e-mail: [email protected] Clinical Dysmorphology: April 2020 - Volume 29 - Issue 2 - p 86-89 doi: 10.1097/MCD.0000000000000299 Buy Metrics Abstract Dystrophic epidermolysis bullosa is a major form of epidermolysis bullosa and may be inherited as an autosomal dominant or recessive trait, with associated mutations in the COL7A1 gene. Here, we describe a consanguineous Pakistani family with four affected individuals suffering from recessive dystrophic epidermolysis bullosa. Exome sequencing of the proband’s DNA revealed a homozygous missense variant (c.8038G>A:p.Gly2680Ser) in COL7A1 which cosegregated with disease in the family. The emergence of this particular glycine substitution in patients from diverse ethnic backgrounds such as China, United Kingdom, Poland, Iran, and Pakistan indicates that this variant most likely constitutes a recurrent mutational hotspot in the COL7A1 gene, rather than a germline mutation present at low levels in the general population. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.