title: Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.
abstract: Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions.
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan; Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Narumi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nishina
authors.forename: Motoharu
authors.initials: M
authors.lastname: Tokimitsu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murata
authors.forename: Fumio
authors.initials: F
authors.lastname: Takada
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D051257:Proto-Oncogene Proteins c-maf / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D051257:Proto-Oncogene Proteins c-maf
keywords: MAF; congenital cataract; iris coloboma; microcornea; whole exome sequencing