title: A novel HSF4 gene mutation causes autosomal-dominant cataracts in a Chinese family.
abstract: Congenital cataracts are a significant cause of visual impairment or blindness in children. One-third of cases estimated to have a genetic cause. We carried out gene analysis and bioinformatics analysis to map the locus and to identify the underlying genetic defect in a 12-member, four-generation Chinese family affected with bilateral congenital cataracts. We screened individuals of the family and discovered a distinct missense mutation in HSF4 (a gene at this locus that encodes teat-shock transcription factor 4). Bioinformatics analysis was used to determine possible changes in the protein structure that could affect the phenotype. Sequencing of the candidate genes showed a heterozygous c.69 G→T change in the heat shock transcription factor 4 (HSF4) gene, which resulted in the substitution of a lysine with an asparagine (p. K23N). This mutation cosegregated with all affected individuals and was not observed in unaffected family members. Bioinformatics analysis indicated that the p. K23N mutation was predicted to be disease causing. This is the first report of the novel missense mutation, c.69 G→T (p. K23N), in exon 3 of the HSF4 locus on 16q21-q22 associated with bilateral congenital cataracts in a Chinese family. This novel mutation could enable propergenetic diagnostics and counseling in affected families and could lead to a better understanding of the structure and function of HSF4 in health and disease.
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Lv
authors.affiliation: Medical Research Center, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, WeiHaiWei People's Hospital, 264200, Shandong China.
authors.forename: Haining
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China lxmlxm66@sina.com.cn.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Beijing University Third Hospital, Beijing, 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D002681:China; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors
keywords: HSF4; congenital cataract family