Sequence variants in nine different genes underlying rare skin disorders in 10 consanguineous families

• Published in: International journal of dermatology Vol. 56; no. 12; pp. 1406 - 1413
• Main Authors: Shah, Khadim, Mehmood, Sabba, Jan, Abid, Abbe, Izoduwa, Hussain Ali, Raja, Khan, Anwar, Chishti, Muhammad S., Lee, Kwanghyuk, Ahmad, Farooq, Ansar, Muhammad, Shahzad, Shaheen, Nickerson, Deborah A., Bamshad, Michael J., Coucke, Paul J., Santos‐Cortez, Regie L. P., Spritz, Richard A., Leal, Suzanne M., Ahmad, Wasim
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2017
• Subjects: 1-Acylglycerol-3-Phosphate O-Acyltransferase - genetics; Aldehyde Oxidoreductases - genetics; Blister - genetics; Collagen Type VII - genetics; Consanguinity; Disorders; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Endonucleases - genetics; Epidermolysis Bullosa - genetics; Epidermolysis Bullosa Dystrophica - genetics; Epidermolysis Bullosa Simplex - genetics; Exome; Female; Flavoproteins - genetics; Follicles; Gene mapping; Gene sequencing; Genes; Genodermatosis; Glands; Homozygosity; Homozygote; Humans; Ichthyosiform Erythroderma, Congenital - genetics; Ichthyosis Vulgaris - genetics; Ichthyosis, Lamellar - genetics; INDEL Mutation; Intermediate Filament Proteins - genetics; Keratin-14 - genetics; Lipid Metabolism, Inborn Errors - genetics; Lipoxygenase - genetics; Male; Membrane Proteins - genetics; Mitochondrial Proteins - genetics; Muscular Diseases - genetics; Nails (Anatomy); Neoplasm Proteins - genetics; Nuclear Proteins - genetics; Pedigree; Periodontal Diseases - genetics; Phenotype; Photosensitivity Disorders - genetics; Porphyria, Variegate - genetics; Protoporphyrinogen Oxidase - genetics; Rare Diseases - genetics; Sebaceous glands; Sjogren-Larsson Syndrome - genetics; Skin; Skin Diseases, Genetic - genetics; Teeth; Tissues; Transcription Factors - genetics; Xeroderma Pigmentosum - genetics
• ISSN: 0011-9059; 1365-4632
• DOI: 10.1111/ijd.13778

Background Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study. Methods Homozygosity mapping, exome, and Sanger sequencing were employed to search for the disease‐causing variants in the 10 families. Results Exome sequencing identified seven homozygous sequence variants in different families, including: c.27delT in FERMT1; c.836delA in ABHD5; c.2453C>T in ERCC5; c.5314C>T in COL7A1; c.1630C>T in ALOXE3; c.502C>T in PPOX; and c.10G>T in ALDH3A2. Sanger sequencing revealed three homozygous variants: c.1718 + 2A>G in FERMT1; c.10459A>T in FLG; and c.92delT in the KRT14 genes as the underlying genetic cause of skin phenotypes. Conclusion This study supports the use of exome sequencing as a powerful, efficient tool for identifying genes that underlie rare monogenic skin disorders.