Low incidence of GIPC3 variants among the prelingual hearing impaired from southern India
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
RESEARCH NOTE
Low incidence of GIPC3 variants among the prelingual hearing impaired from southern India MURUGESAN KALAIMATHI, MAHALINGAM SUBATHRA, JUSTIN MARGRET JEFFREY , MATHIYALAGAN SELVAKUMARI, JAYASANKARAN CHANDRU , NARASIMHAN SHARANYA, VANNIYA S. PARIDHY and C. R. SRIKUMARI SRISAILAPATHY* Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Chennai 600 113, India *For correspondence. E-mail: [email protected]. Received 24 October 2019; revised 24 June 2020; accepted 24 August 2020 Abstract. The broad spectrum of causal variants in the newly discovered GIPC3 gene is well reflected in worldwide studies. Except for one missense variant, none of the reported variants had reoccurred, thus reflecting the intragenic heterogeneity. We screened all the six coding exons of GIPC3 gene in a large cohort of 177 unrelated prelingual hearing impaired after excluding the common GJB2, GJB6 nuclear and A1555G mitochondrial variants. We observed a single homozygous pathogenic frameshift variant c.685dupG (p.A229GfsX10), accounting for a low incidence (0.56%) of GIPC3 variants in south Indian population. GIPC3 being a rare gene as a causative for deafness, the allelic spectra perhaps became much more diverse from population to population, thus resulting in a minimal recurrence of the variants in our study, that were reported by authors from other parts of the globe. Keywords.
prelingual deafness; c.685dupG; consanguinity; south India; GIPC3 gene.
Introduction Deafness variants are recurrently identified in GJB2, SLC26A4, TMC1, OTOF and CDH23 genes (Hilgert et al. 2009; Sloan-Heggen et al. 2016; Azaiez et al. 2018). Some gene variants are exceedingly rare and do not occur at same frequencies across ethnicities. This work focusses on one such gene, GAIP-interacting protein C terminus-3 (GIPC3) located at 19p13.3. Although GIPC3 was first localized (DFNB95) in an Indian family with recessive inheritance using linkage approach (Charizopoulou et al. 2011), it was not well explored later. Most of the studies on GIPC3 were in Asian populations predominately from Pakistan (table 1). GIPC3 extends over 8 kbp (six coding exons) encoding 312 amino acids. Involvement of GIPCs in signalling, trafficking and recycling of receptor tyrosine kinases, G-protein coupled receptors, integrins and other transmembrane proteins are very well established. GIPCs are proteins with central
PDZ domain and flanking conserved GIPC homology (GH1 and GH2) domains (Katoh 2002). In the past two decades, tremendous efforts have been made to unravel the rich locus heterogeneity with respect to autosomal recessive nonsyndromic hearing loss (ARNSHL) on chromosome 19. Telomeric region of chromosome 19p includes three closely linked hearing loss loci DFNB72, DFNB81 and DFNB68 (Katoh 2013). Germline variants of human GIPC3 have been reported in ARNSHL involving DFNB15 (Chen et al. 1997), DFNB72 (Rehman et al. 2011), and DFNB95 (Charizopoulou et al. 2011). Studies suggest tha
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