A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.

Autor: Palombo F; Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy., Al-Wardy N; College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Ruscone GA; Laboratory of Molecular Anthropology & Centre for Genome Biology, Department BiGeA University of Bologna, Bologna, Italy., Oppo M; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.; Dipartimento di Scienze Biomediche, University of Sassari, Sassari, Italy., Kindi MN; College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Angius A; 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., Al Lamki K; College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Girotto G; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.; Division of Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar., Giangregorio T; Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy., Benelli M; Department Laboratory, Careggi University Hospital, Firenze, Italy., Magi A; Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy., Seri M; Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy., Gasparini P; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.; Division of Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar., Cucca F; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.; Dipartimento di Scienze Biomediche, University of Sassari, Sassari, Italy., Sazzini M; Laboratory of Molecular Anthropology & Centre for Genome Biology, Department BiGeA University of Bologna, Bologna, Italy., Al Khabori M; Department of ENT, Al Nahda Hospital, Ministry of Health, Muscat, Oman., Pippucci T; Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy., Romeo G; Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2017 Feb; Vol. 62 (2), pp. 259-264. Date of Electronic Publication: 2016 Oct 13.
DOI: 10.1038/jhg.2016.120
Abstrakt: 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.
Databáze: MEDLINE
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