Mutation Detection In Coding Regions Of NLGN4 Gene In Mental Retardation Patients And Pedigrees Of Qinba Mountain Area

Mental retardation (MR) is one kind of common mental disorder, characterized by low intellectual function and significant limitations in adaptive functioning that manifest before the age of 18 years. The Qinba mountain area is one of the higher MR prevalence areas in China. So,it is a very important and practical to make clear the genetic pathogeny of MR in Qinba area for the further study on prevention and control.Our group had suggested a positive association between the gene NLGN4 and MR in the Chinese children from Qinba Mountain area in advanced research,but the exact pathogenic locis and pathogenic types will need further study. Neuroligin-4(NLGN4)gene belongs to the neuroligin family,is a postsynaptic cell-adhesion molecules that interact with neurexin to modulate percentage of excitatory and inhibitory synapse and play an important role in Synapse formation and remodeling on the central nervous system.To further explore the relation between point mutation of gene NLGN4 and local MR,6 exon in NLGN4 were detected by the technoledgy of PCR-DGGE and DNA sequencing in 400 MR patients and pedigrees in Qinba Mountains area.Results are as follows:(1) Two type of single base missense mutation were detected in two MR patients,one is c.544G>A (p.Gly182Ser)has been found in exon 3 of MR337 case,another mutation is c.1172C>T (p.Thr391Met) in exon 5 of MR149 case. Detected the two loci in 200 normal people has show that these two missense mutation were not single nucleotide Polymorphisms(SNP).(2) The pedigree of MR337 were detected in exon 3 and did not found the mutation c.544G>A (p.Gly182Ser);MR149 pedigree were detected in exon 5 and found the mutation c.1172C>T (p.Thr391Met) in 4 female cousins of MR149 case.(3)This study used bioinformatics software predicted and analysised the two mutation p. Gly182Ser, p.Thr391Met in protein structure and function.MEGA6 analysis displayed two amino acid in different species kept highly conservative; PSIPRED software analyzed the pathogenic mechanism in protein structure and predicted that both mutations caused protein secondary structure with more of alpha helix and beta fold changed, which may lead to the function deficit of the protein structure domain.Polyphen2 and SIFT software provided function forecast on mutation protein and displayed two mutations were harmful,which may had caused protein function changed.Our research suggested that the mutations p.G ly182Ser, p.T hr391Met of NLGN4 gene may be a high risk factor of MR in Qinba mountain area.But,The pathogenic mechanism of single base mutations to MR need to collect blood of patients for the after study on gene transcription level,protein expression level and cellular level.