A Novel Pathologic Variant in OTOF in an Iranian Family Segregating Hereditary Hearing Loss

Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery
Mohammad Amin TabatabaiefarJavad Mohammadi-Asl

Abstract

Objective Hearing loss (HL) is the most common sensory-neural defect and the most heterogeneous trait in humans, with the involvement of >100 genes, which make a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Study Design Descriptive experimental study. Setting Diagnostic laboratory. Subjects and Methods A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in a family with multiple individuals with HL. As the first tier, GJB2 was sequenced, and genetic linkage analysis of DFNB1A/B was performed to rule out the most common cause of the disease. Targeted NGS was used to unravel the molecular etiology of the disease in the HL-associated genes in the proband. Two homozygous variants remained in OTOF after proper filtration. Cosegregation and in silico analysis were done. Preimplantation genetic diagnosis (PGD) was accomplished via linkage analysis and direct sequencing of the pathogenic variant. Results Clinical evaluations suggested autosomal recessive nonsyndromic HL. Two homozygous variants, c.367G>A (p.Gly123Ser) and c.1392+1G>A, were identified in cis status. c.1392+1G>A met the criteria for being pathogen...Continue Reading

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Citations

Aug 31, 2020·Journal of Clinical Laboratory Analysis·Fatemeh BitarafanMasoud Garshasbi
Dec 26, 2019·International Journal of Pediatric Otorhinolaryngology·Raja A H KuchayMustafa Tekin

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Methods Mentioned

BETA
PCR
Exome Sequencing

Software Mentioned

SIFT
FATHMM
BWA
Picard
ConSurf
PROVEAN
BDGP
GATK
DNASTAR
OtoSCOPE

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