Detection of disease-causing gene in a Hui congential cataract pedigree by exon combined target region capture sequencing chip / 中华实验眼科杂志

ABSTRACT

Background Congenital cataract is an important cause of blindness and amblyopia in children,and about 50％ of congenital cataract is hereditary.Objective The aim of this study was to determine the diseasecausing gene of one Hui congenital cataract pedigree by using exon combined target region capture sequencing chip of eye diseases.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and followed Declaration of Helsinki.One Hui congenital cataract pedigree was recruited in Ningxia Eye Hospital in 2011.All the disease history of the members in this family were collected and recorded,and the eye examinations were performed.The peripheral blood specimens were collected from family members and 300 healthy individuals for the extraction of DNA.Exon combined target region capture sequencing chip of eye diseases was used to screen the candidate diseasecausing mutations,then PCR and direct sequencing were used to confirm the disease-causing mutations.Results This H ui family included 61 members of 6 generations,and 18 patients were diagnosed in serial 5 passages,conforming to autosomal dominant inheritance pattern.Among 18 cataract patients,7 individuals were associated with nystagmus and strabismus,and 4 patients had high myopia.Eight candidate pathogenetic mutations were detected by exon combined target region capture sequencing chip of eye diseases and bioinformatics method,with 5 mutations in noncoding regions and 3 in coding regions.The mutation P24T of CYRGD gene was confirmed as pathogenic mutation of this pedigree by using PCR and direct sequencing methods.These mutations co-segregated with affected members of the family,and the mutations were not found in the unaffected family members and 300 unrelated controls.Conclusions P24T of CYRGD gene mutation is confirmed as pathogenic mutation of this pedigree.Exon combined target region capture sequencing chip provides a new approach to detect disease-causing mutations of congenital cataract with diversity clinical phenotypes.