Khadim Shah1,2, Sabba Mehmood1, Abid Jan1,3, Izoduwa Abbe4, Raja Hussain Ali1,5, Anwar Khan6, Muhammad S Chishti6, Kwanghyuk Lee4, Farooq Ahmad1, Muhammad Ansar1,4, Shaheen Shahzad7, Deborah A Nickerson8, Michael J Bamshad8, Paul J Coucke5, Regie L P Santos-Cortez4,9, Richard A Spritz2,10, Suzanne M Leal4, Wasim Ahmad1. 1. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. 2. Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, CO, USA. 3. Department of Biotechnology & Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan. 4. Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. 5. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. 6. Department of Biochemistry, Hazara University, Mansehra, Pakistan. 7. Department of Biotechnology & Bioinformatics, International Islamic University, Islamabad, Pakistan. 8. Department of Genome Sciences, University of Washington, Seattle, Washington, USA. 9. Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, USA. 10. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Abstract
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.
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.
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