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

Publication date: June 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 97
Author(s): Farah Talebi, Farideh Ghanbari Mardasi, Javad Mohammadi Asl, Amir Hooshang Bavarsad, Saeed Tizno
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.



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