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.

Sporadic and Familial Congenital Cataracts: Mutational Spectrum and New Diagnoses Using Next‐Generation Sequencing

“…B). Up until this report, five mutations have been found in the basic region of MAF , in patients with isolated ocular abnormalities, all clustered around the b‐zipper domain [Jamieson et al., , ; Vanita et al., ; Hansen et al., ; Narumi et al., ] (Fig. B).…”

Novel missense mutation in the bZIP transcription factor, MAF, associated with congenital cataract, developmental delay, seizures and hearing loss (Aymé-Gripp syndrome)

“…They also reported a variant in the DNA-binding domain of MAF (p.(Arg288Pro)) in a three generations family with lamellar cortical and nuclear pulverulent cataract, microcornea, and iris coloboma. Narumi et al [32] identified a MAF variant (p.(Gln303Leu)) through whole exome sequencing in a family with phenotypically variable congenital cataract (lamellar or anterior polar with microcornea and iris coloboma). The affected proband was diagnosed with lamellar cataract without any other eye malformation with language development delay and autism.…”

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract

“…The development of molecular genetics and technology has facilitated extensive investigations into the familial pedigree of congenital cataract via the use of new sequencing technologies such as whole genome sequencing and WES (Narumi et al, 2014). Consequently, this allows us to elucidate the pathogenesis of sex-linked congenital cataract at a molecular level and study the gene-gene and gene-environment interactions, which in turn could help provide comprehensive patient services.…”