title: Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages.
abstract: Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epidermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheritance. The mutation profile attests to the impact of consanguinity in these families.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Vahidnezhad
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Youssefian
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Kawsar Human Genetics Research Center, Tehran, Iran.
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Saeidian
authors.affiliation: Department of Dermatology, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Sotoudeh
authors.affiliation: Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nikoo
authors.initials: N
authors.lastname: Mozafari
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran; Kawsar Human Genetics Research Center, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Abiri
authors.affiliation: Paediatric Urology Research Center, Department of Urology, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abdol-Mohammad
authors.initials: AM
authors.lastname: Kajbafzadeh
authors.affiliation: Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Barzegar
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Molecular Medicine, Sapienza University, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: Jouni.Uitto@Jefferson.edu.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D024143:Collagen Type VII / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics*; D018604:Epitope Mapping; D005192:Family Health; D005260:Female; D005843:Geography; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007492:Iran; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C569053:COL7A1 protein, human; D024143:Collagen Type VII