A Novel GPR143 Mutation In A Chinese Family Of Congenital Nystagmus

Objective:1. To analysis the clinical features and genetic characteristics in a Chinese family with X chromosome chain recessive congenital nystagmus.And to extraction genome DNA of family members,establish the library of clinical data and blood specimens.2. To screen the virulence genes and pathogenic mutations in CN-HN001 family members.3. To preliminary analysis of the encoded protein functions on pathogenic mutations.Methods:1. Collect the basic data of CN-HN001 family:clinical information, prevalence, genetic conditions, sign the informed consent,ophthalmic examination.Draw genetic pedigree map of the disease according to their genetic information. Take a peripheral venous blood and extraction of genomic DNA and saved under condition of-80 ? after accreditation.2. Using high-throughput sequencing with exome capture to test the CN-HN001 family proband's whole genome DNA samples and comparing genomic DNA sequences in the database, screening out the pathogenic genes from the candidate genes and analyze the positioning of pathogenic mutations.3. Using Sanger sequencing technology to validated the suspected pathogenic mutations of the proband to confirm reliability of the pathogenic mutations.Subsequently,the pathogenic mutations were validated in CN-HN001 family members and 100 normal unaffected individuals using Sanger sequencing.4. The impact of causative gene encoding the protein structure would be analyzed according to the pathogenic mutations.Results:1. According to the genetic characteristics and clinical phenotype the CN-HN001 family was identified as an X chromosome chain recessive Congenital Nystagmus family.The whole were extracted from the blood and identify its purity standards. Specification established pedigree clinical database and blood specimens library.2. The results on the test of CN-HN001 family proband's whole genome DNA samples showed hemizygous splicing mutation c.360+5 G> T was in GPR143 gene.3. The results of Sanger sequencing confirmed that the hemizygous splicing mutation does exist.The validation in CN-HN001 family members showed the separation of genotype and phenotype in CN-HN001 family for the mutation c.360+5 G> T. This result confirmed that the mutation did lead CN in the family.The verification in 100 normal unaffected individuals showed that this mutation sites do not exists on them,which confirmed the CN pathogenic mutation sites.4. GPR143 genetic mutations resulting in its coding protein, amino acid type change, resulting in pathogenicity.Conclusion:1. The family was a X chromosome chain recessive Congenital Nystagmus family;Family clinical database and the establishment of the blood bank has provided the safeguard for subsequent research.2. This study found a splicing mutation c.360+5 G> T on GPR143 gene in Chinese congenital nystagmus family and successful positioning of the site.There was no report about this mutation from any major genome database.This outcome enriched the mutation spectrum of GPR143 gene.