Identification of Novel PTPRQ and MYO1A Mutations in An Iranian Pedigree with Autosomal Recessive Hearing Loss.

Autosomal recessive non-syndromic hearing loss (ARNSHL) is defined as a genetically heterogeneous disorder. The aim of the present study was to screen for pathogenic variants in an Iranian pedigree with ARNSHL. Next-generation targeted sequencing of 127 deafness genes in the proband detected two novel variants, a homozygous missense variant in PTPRQ (c.2599 T>C, p.Ser867Pro and a heterozygous missense variant in MYO1A (c.2804 T>C, p.Ile935Thr), both of which were absent in unaffected sibs and two hundred unaffected controls. Our results suggest that the homozygous PTPRQ variant maybe the pathogenic variant for ARNSHL due to the recessive nature of the disorder. Nevertheless, the heterozygous MYO1A may also be involved in this disorder due to the multigenic pattern of ARNSHL. Our data extend the mutation spectrum of PTPRQ and MYO1A, and have important implications for genetic counseling in unaffected sibs of this family. In addition, PTPRQ and MYO1A pathogenic variants have not to date been reported in the Iranian population.

Identification of a novel missence mutation in FGFR3 gene in an Iranian family with LADD syndrome by Next-Generation Sequencing.

Lacrimo-auriculo-dento-digital syndrome (LADD) is a multiple congenital anomaly and a genetically heterogeneous disorder. The aim of this study was to identify the pathogenic gene in an Iranian family with LADD syndrome and review the literature on reported mutations that involved in pathogenesis of LADD syndrome. One novel variant, c.1882 G > A, in fibroblast growth factor receptor 3 (FGFR3) was identified by next generation sequencing and Sanger sequencing. The heterozygous FGFR3 c.1882 G > A variant results in substitution of aspartic acid with asparagine at amino acid 628 (p.D628N) and co-segregated with the phenotype in the LADD family. Our findings suggest that the heterozygous FGFR3 c.1882 G > A variant might be the pathogenic mutation, because this amino acid is conserved in several species. Our data extend the mutation spectrum of the FGFR3 gene and have important implications for genetic counseling for the families. This is the second report of FGFR3 involvement in syndromic deafness in humans, and confirms the gene's positive role in inner ear development. In addition, this is the first FGFR3 mutation recognized in the Iranian LADD family.