Whole Exome Sequencing Identifies <i>ABHD14A</i> and <i>MRNIP</i> as Novel Candidate Genes for Developmental Language Disorder
收藏资源简介：
Developmental language disorder (DLD) is a neurodevelopmental disorder involving impaired languageabilities. Its genetic etiology is heterogeneous, involving rare variations in multiple susceptibility loci.However, family-based studies on gene mutations are scarce. We performed whole-exome sequencingof a first-time-described Tunisian-family with DLD. Analyses of segregation patterns with stringentfiltering of the exome data identified disease-causing compound heterozygous variants. In the MRNIPgene, two variants were detected including a synonymous low-frequency variant c.345G > C and anonsense rare variant c.112G > A predicted pathogenic. In the ABHD14A gene, four variants wereidentified including a rare missense variant c.689T > G and three splice-site variants c.70–8 C > T,c.282–25 A > T and c.282-10G > C with low-frequency MAF < 5%. Complementary analyses showed thatthese variants are predicted pathogenic and the missense variant Leu230Arg significantly affects thestability and structure modelling of the ABHD14A protein. Biological functions and interconnectionsanalyses predicted the potential roles of ABHD14A and MRNIP in neuronal development pathways.These results suggest ABHD14A and MRNIP, as putative candidate genes for DLD susceptibility. Ourfindings reveal the involvement of novel candidate genes in the genetic etiology of DLD and explorethe potential future utility of WES in the diagnosis of such complex disorders.
