Open AccessIdentification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next‐generation sequencing
Author(s) -
Bitarafan Fatemeh,
Seyedena Seyed Yousef,
Mahmoudi Mahdi,
Garshasbi Masoud
Publication year - 2020
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23544
Subject(s) - sanger sequencing , hearing loss , pedigree chart , genetics , gene , loss function , genetic counseling , compound heterozygosity , mutation , genetic testing , biology , genetic heterogeneity , heterozygote advantage , medicine , phenotype , audiology , genotype
Background The extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL). Methods After excluding mutations in the most common ARNSHL gene, GJB2 , by Sanger sequencing, genetic screening for a panel of genes responsible for hereditary hearing impairment performed in 9 individuals with ARNSHL from unrelated Iranian consanguineous pedigrees. Results One compound heterozygote and eight homozygote variants, of which five are novel, were identified: CDH23: p.(Glu1970Lys), and p.(Ala1072Asp), GIPC3 :p.(Asn82Ser), and (p.Thr41Lys), MYO7A :p.[Phe456Phe]; p.[Met708Val], and p.(Gly163Arg), TECTA :p.(Leu17Leufs*19), OTOF: c.1392+1G>A, and TRIOBP :p.(Arg1068*). Sanger sequencing confirmed the segregation of the variants with the disease in each family. Conclusion Finding more variants and expanding the spectrum of hearing impairment mutations can increase the diagnostic value of molecular testing in the screening of patients and can improve counseling to minimize the risk of having affected children for at risk couples.