The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family

BMC Medical Genetics
Michaela A H HofrichterBarbara Vona

Abstract

Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family. Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed. The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change. In summary, we report the t...Continue Reading

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Citations

Sep 15, 2020·Frontiers in Cellular and Infection Microbiology·Gunanidhi Dhangadamajhi, Shailja Singh
Jan 27, 2021·Human Genetics·Barbara VonaHamid Galehdari

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Methods Mentioned

BETA
exome sequencing
amino acid exchange
nucleotide exchange

Software Mentioned

MaxEntScan
Coot
Gensearch
Alamut
NNSPLICE
Phyre2 ( Homology / analogY Recognition Engine
Alamut Visual biosoftware
Human
Splicing Finder
SpliceSiteFinder

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