title: A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.
abstract: The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Palombo
authors.affiliation: College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Nadia
authors.initials: N
authors.lastname: Al-Wardy
authors.affiliation: Laboratory of Molecular Anthropology & Centre for Genome Biology, Department BiGeA University of Bologna, Bologna, Italy.
authors.forename: Guido Alberto Gnecchi
authors.initials: GA
authors.lastname: Ruscone
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.|Dipartimento di Scienze Biomediche, University of Sassari, Sassari, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Oppo
authors.affiliation: College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Mohammed Nasser Al
authors.initials: MN
authors.lastname: Kindi
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.|Center for Advanced Studies, Research, and Development in Sardinia (CRS4), Parco Scientifico e Tecnologico della Sardegna, Pula, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Angius
authors.affiliation: College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Khalsa
authors.initials: K
authors.lastname: Al Lamki
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.|Division of Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Girotto
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Giangregorio
authors.affiliation: Department Laboratory, Careggi University Hospital, Firenze, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Benelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Magi
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.|Division of Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.|Dipartimento di Scienze Biomediche, University of Sassari, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.affiliation: Laboratory of Molecular Anthropology & Centre for Genome Biology, Department BiGeA University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sazzini
authors.affiliation: Department of ENT, Al Nahda Hospital, Ministry of Health, Muscat, Oman.
authors.forename: Mazin
authors.initials: M
authors.lastname: Al Khabori
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pippucci
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D003241:Consanguinity; D003638:Deafness / Q000235:genetics*; D059472:Exome / Q000235:genetics; D018703:Founder Effect; D016368:Frameshift Mutation / Q000235:genetics*; D020440:Gene Duplication / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009218:Myosins / Q000235:genetics*; D009850:Oman; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C485245:MYO15A protein, human; D009218:Myosins