Functional consequences of Genetics variant in TMC1 and TMC2 within a United Arab Emirates family with Pre-lingual hearing loss
Mutery, Abdullah (University of Sharjah. Department of Applied Biology)
Mohamed, Kamal Eldin Walaa (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mahfood, Mona (University of Sharjah. Department of Applied Biology)
Chouchen, Jihen (University of Sharjah)
Tlili, Abdelaziz (University of Sharjah. Research Institute of Sciences & Engineering)

Data:	2023
Resum:	Hearing loss (HL) is the most prevalent sensory disorder whose etiology comes from environmental and/or genetic factors. Approximately 60 % of HL cases are due to mutations in genes responsible for maintaining a normal hearing function. Despite the monogenic inheritance of hereditary hearing loss (HHL), its diagnosis is challenging as both clinical and genetic heterogeneity characterizes it. Through the development of next-generation sequencing (NGS) techniques, the number of identified mutations responsible for HHL has increased exponentially during the last decade. Mutations in the TMC1 have been reported in several patients with nonsyndromic hereditary hearing loss (NSHHL), more precisely in cases with an autosomal recessive inheritance pattern. In this study, we conducted whole-exome sequencing (WES) analysis of a United Arabs Emirates (UAE) family with autosomal recessive nonsyndromic hearing loss (ARNSHL). This analysis revealed segregation of the TMC1 missense mutation c. 596A > T (p. Asn199Ile) with the disease. Bioinformatics analysis supported the pathogenic effect of this mutation and predicted its impact at the proteomics level. Molecular docking analysis of TM C2WT, TMC2 R123K, TMC2 Q205R, and TMC2 R123K + Q205R. Finally, protein docking results suggest a role for TMC2 variants in the phenotypic variability observed within the investigated family.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Non-syndromic Hearing Loss ; Whole-exome sequencing ; TMC1 ; C.596a > T mutation ; Phenotypic variability ; Protein docking ; HL, Hearing Loss ; HHL, Hereditary Hearing Loss ; NGS, Next Generation Sequencing ; NSHHL, Nonsyndromic Hereditary Hearing Loss ; WES, Whole-Exome Sequencing ; UAE, United Arabs Emirates ; ARNSHL, Autosomal Recessive Nonsyndromic Hearing Loss ; GATK, Genome Analysis Toolkit ; GnomAD, Genome Aggregation Database ; PCR, Polymerase Chain Reaction
Publicat a:	Saudi Journal of Biological Sciences, Vol. 30, Issue 2 (February 2023) , art. 103520, ISSN 2213-7106

DOI: 10.1016/j.sjbs.2022.103520
PMID: 36568409

10 p, 2.8 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats