Mutation of 22q11.2-q12.1 gene in a family with autosomal dominant congenital membranous cataract
- VernacularTitle:先天性膜性白内障一家系致病基因的遗传分析
- Author:
Yuan, FANG
;
Li, FEIFENG
;
Liu, WEI
;
Liu, HUA
;
Ji, JIAN
;
Ma, XU
- Publication Type:Journal Article
- Keywords:
congenital cataract;
autosomal dominant;
membranous cataract;
microsatellite markers
- From:Chinese Ophthalmic Research
2009;27(12):1100-1103
- CountryChina
- Language:Chinese
-
Abstract:
Objective Autosomal dominant congenital cataract (ADCC) is a common heredit disease.Some known genes and mutated loci related to ADCC have been found.The present study provides other disease-causing genes in the ADCC family.This study was to identify the genetic defect in four generations of a Chinese family with autosomal dominant congenital membranous cataracts and demonstrate the functional analysis of a candidate gene in the family.MethodsThe family with hereditary cataract was recruited from the Tianjin Medical University Eye Center.The family history was collected and recorded.Clinical and ophthalmologic examinations were performed on 6 affected and 14 unaffected family members and periphery blood samples were collected from all of the subjects for genomic DNA preparation.The members were genotyped with microsatellite markers at loci associated with cataracts.Multiplex polymerase chain reaction (PCR) was carried out with microsatellite markers near to candidated loci related to congenital cataracts.PCR products from each DNA sample were separated on a polyarcylamide gel and analyzed.Exclusion analysis was performed by allele sharing analysis and gene sequencing.This trail was approved by the Human Research Ethics Committee of this hospital.The oral informed consent was obtained from all of the subjects before the initiation of this trial.ResultsThe hereditary characteristic of this family was in accordance with the autosomal dominant inheritance with a gene penetrance 100%.Affected members of the family were diagnosed with membranous cataracts without other ocular symptom.The disease-causing gene locus were mapped to 22q11.2-q12.1 at a size of about 2.4 Mbp.The multiple-sequence alignments of complete coding region and splice site of CRYBB1,CRYBB2,CRYBB3,CRYBA4 were obtained but no mutation was found in this study.CRYBB1,CRYBB2,CRYBB3,CRYBA4 were screened by directly sequencing.ConclusionAll known ADCC loci have been excluded from the family.Further study should be carried out to screen other relevant genes or loci in patients with ADCC.The pathogenic gene in the family should be identified through extensive scanning of genes,and a new disease-causing gene may exist in this family.
