Analysis Of PCDH15 Gene Mutation And Prenatal Diagnosis In A Pedigree Affected With Usher Syndrome Type 1

ObjectiveTo identify the causative gene and locus of a congenital deafness pedigree and subsequently carry out a prenatal diagnosis of a fetus in the 18^thweek of gestation.MethodsCollection of clinical data of Usher syndrome family:Medical history and family history of this family were collected in details.A pedigree figure was drawn.The complete genomic DNA was extracted from the peripheral blood.Next-generation sequencing（NGS）technology was used to analyze deafness-related genes by capturing the whole exons and adjacent intronic regions.Mutation sites were selected according to mutation interpretation rules of American University Medical Genetics（ACMG）,genetic significance and clinical feature coincidence degree,and the mutations that are consistent in the three aspects are pathogenic.Suspected mutations were verified by Sanger sequencing.Based on the positive result of the genetic testing,the prenatal diagnosis of the fetus was attained.ResultsThe proband was detected to carry a compound heterozygous mutations in the protocadherin related 15（PCDH15）gene c.3490＿3491ins A（p.M1164Nfs*12）of exon 27 and c.4115del G（p.G1372Efs*4）of exon 31 on chromosome 10.The c.3490＿3491ins A frameshift mutation originated from the father and the c.4115del G from the mother,which led to the early termination of protein translation.c.4115del G and c.3490＿3491ins A were identified as novel mutations,predicted to be pathogenic by ACMG guidelines.The proband was diagnosis as Usher syndrome 1（USH1）,his parents presented normal phenotypes.USH1 was an autosomal recessive inheritance in this family.In addition,our prenatal diagnosis showed that the fetus carried the same compound heterozygosity of PCDH15 as the proband.ConclusionsThe deafness phenotype of our patient may be attributed to compound heterozygous mutations of PCDH15 at loci c.3490＿3491ins A and c.4115del G.Identification of two novel PCDH15 mutations has enriched the mutational spectrum of the PCDH15 gene.