Genome sequencing identifies coding and non-coding variants for non-syndromic hearing loss.

Autor: Ramzan M; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Duman D; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.; Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey., Hendricks LCP; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Guo S; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Mutlu A; Department of Otorhinolaryngology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey.; Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey., Kalcioglu MT; Department of Otorhinolaryngology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey.; Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey., Seyhan S; Department of Medical Genetics, Faculty of Medicine, Uskudar University, Istanbul, Turkey., Carranza C; Institute for Research on Genetic and Metabolic Diseases, INVEGEM, Guatemala City, Guatemala., Bonyadi M; Faculty of Natural Sciences, Center of Excellence for Biodiversity, University of Tabriz, Tabriz, Iran., Mahdieh N; Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran., Yildirim-Baylan M; Department of Otorhinolaryngology, Dicle University School of Medicine, Diyarbakir, Turkey., Figueroa-Ildefonso E; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.; Universidad Peruana Cayetano Heredia, Lima, 15102, Peru., Alper O; Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya, Turkey., Atik T; Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey., Ayral A; Department of Otolaryngology, Faculty of Medicine, Yuzuncu Yıl University, Van, Turkey., Bozan N; Department of Otolaryngology, Faculty of Medicine, Yuzuncu Yıl University, Van, Turkey., Balta B; Department of Medical Genetics, Kayseri Training and Research Hospital, Kayseri, Turkey., Rivas C; Molecular Genetic Lab, FFAA Hospital, Quito, Ecuador., Manzoli GN; Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil., Huesca-Hernandez F; Genetics and Genomic Medicine Service. National Institute of Rehabilitation, Mexico City, Mexico., Kuchay RAH; Department of Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, J&K, India., Durgut M; Kocaeli University Otorhinolaryngology Department- Audiology Unit, İzmit, Turkey., Bademci G; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Tekin M; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. MTekin@med.miami.edu.; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA. MTekin@med.miami.edu.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2023 Oct; Vol. 68 (10), pp. 657-669. Date of Electronic Publication: 2023 May 22.
DOI: 10.1038/s10038-023-01159-9
Abstrakt: Hearing loss (HL) is a common heterogeneous trait that involves variants in more than 200 genes. In this study, we utilized exome (ES) and genome sequencing (GS) to effectively identify the genetic cause of presumably non-syndromic HL in 322 families from South and West Asia and Latin America. Biallelic GJB2 variants were identified in 58 probands at the time of enrollment these probands were excluded. In addition, upon review of phenotypic findings, 38/322 probands were excluded based on syndromic findings at the time of ascertainment and no further evaluation was performed on those samples. We performed ES as a primary diagnostic tool on one or two affected individuals from 212/226 families. Via ES we detected a total of 78 variants in 30 genes and showed their co-segregation with HL in 71 affected families. Most of the variants were frameshift or missense and affected individuals were either homozygous or compound heterozygous in their respective families. We employed GS as a primary test on a subset of 14 families and a secondary tool on 22 families which were unsolved by ES. Although the cumulative detection rate of causal variants by ES and GS is 40% (89/226), GS alone has led to a molecular diagnosis in 7 of 14 families as the primary tool and 5 of 22 families as the secondary test. GS successfully identified variants present in deep intronic or complex regions not detectable by ES.
(© 2023. The Japan Society of Human Genetics.)
Databáze: MEDLINE
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