A novel homozygous mutation in HSF4 causing autosomal recessive congenital cataract.
Cataract is defined as opacity in the crystalline lens and congenital cataract occurs during the first year of life. Until now, mutations of more than 50 genes in congenital cataract have been reported with various modes of inheritance. Among them, HSF4 mutations have been reported in autosomal dominant, autosomal recessive and age-related forms of cataract. The inheritance patterns of these mutations depend on their mutational positions in HSF4: autosomal dominant or recessive mutations are respectively found either in a DNA-binding domain or in (or downstream of) hydrophobic repeats. Here we report a novel homozygous HSF4 mutation (c.521T>C, p.Leu174Pro) in two affected sibs of an Iranian consanguineous family using whole exome sequencing. The mutation is predicted as highly pathogenic by in silico analysis (SIFT, Polyphen2 and MutationTaster) and is not found in any of control databases. This mutation is located in a hydrophobic repeat of the HSF4 protein, which is consistent with the mode of inheritance as an autosomal recessive trait.
Medical Genetics Center of Genome, Isfahan, Iran.
Mahdiyeh
M
Behnam
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Eri
E
Imagawa
Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Ahmad Reza Salehi
AR
Chaleshtori
Medical Genetics Center of Genome, Isfahan, Iran.
Firooze
F
Ronasian
Division of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Mansoor
M
Salehi
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Noriko
N
Miyake
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Naomichi
N
Matsumoto
D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D000076249:Heat Shock Transcription Factors; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors