A number sign (#) is used with this entry because of evidence that multiple types of cataract (CTRCT21) are caused by heterozygous mutation in the MAF gene (177075) on chromosome 16q23.

Mutations in the MAF gene have been found to cause multiple types of cataract, which have been described as cortical pulverulent, lamellar, nuclear, nuclear pulverulent, nuclear stellate, anterior polar, anterior subcapsular, posterior subcapsular, and cerulean. In some cases, the cataracts are of juvenile onset.

The preferred title of this entry was formerly 'Cataract, Pulverulent, Juvenile-Onset,' with an 'Included' title/symbol of 'Cataract, Congenital, Cerulean Type, 4; CCA4.'

Jamieson et al. (2002) reported a family in which autosomal dominant juvenile-onset cataract segregated in 3 generations. The cataracts were cortical pulverulent opacities in a lamellar distribution. Nuclear pulverulent opacities were present in 2 cases. There was later progression with posterior subcapsular opacification that necessitated surgery in adult life. In addition to cataract, 2 of the 5 affected individuals had microcornea, and 1 also had bilateral iris colobomas.

Vanita et al. (2006) reported a 3-generation family in which 12 of 20 members had bilateral cataract; 6 affected individuals also had microcornea. The cataracts consisted of fine cerulean opacities occupying the superficial layer of lens fibers under the anterior and posterior capsule. The opacities varied in size, being larger toward the center where they were connected to the anterior and posterior sutures. The cataracts were progressive, with more prominent changes seen in older individuals. No coloboma or microphthalmia was observed in this family.

Hansen et al. (2007) studied a family in which 4 members spanning 3 generations had cataract and microcornea; 1 patient also had iris coloboma. The maternal grandmother had congenital cataracts that were surgically removed at 47 years of age; the mother had dense posterior polar cataracts diagnosed at 5 months of age, with surgery postponed to age 21 years because visual acuity was sufficient; and her 2 children had nuclear cataracts, which were described as dense zonular (lamellar) in the sister and 'star-shaped' in the brother. The mother also had iris coloboma of the right eye.

Narumi et al. (2014) reported a Japanese family in which 6 members spanning 3 generations had congenital cataract, 3 of whom also had microcornea; 1 patient exhibited iris coloboma. The 5-year-old male proband had lamellar cataracts diagnosed in the neonatal period, with removal at 3 months. He also exhibited delayed language development and was diagnosed with autism spectrum disorder (ASD; see 209850) at 4 years of age. Because he had abnormal lower incisors and a bifid uvula, Nance-Horan syndrome (NHS; 302350) was suspected, but analysis of the NHS gene (300457) was negative. His mother and maternal grandmother had bilateral cataracts removed in childhood, and a maternal aunt and 2 cousins also had congenital cataracts. Other ocular features in this family included mild macular hypoplasia in 1 patient and retinal detachment in another.

Jamieson et al. (2002) identified a family in which ocular developmental abnormalities cosegregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. Individuals with the balanced translocation had juvenile-onset progressive cataracts, involving widespread pulverulent opacities with anterior and posterior sutural densities. Individuals with an unbalanced karyotype had a more severe ocular phenotype, including progression to total cataracts and severe myopia, opaque corneas, and Peters anomaly with microphthalmia; they also had dysmorphic facial features and developmental delay, and 1 died soon after birth due to laryngeal stenosis. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of the MAF gene; in addition, it transected the common fragile site FRA16D (see 605131), providing a molecular demonstration of a germline break in a common fragile site.

Vanita et al. (2006) performed linkage analysis in a 3-generation family segregating autosomal dominant cerulean congenital cataract, using DNA samples from 12 affected and 8 unaffected family members. A maximum lod score of 3.9 (theta = 0.0) was obtained with 3 markers on chromosome 16, D16S3049, D16S3040, and D16S511. Multipoint and haplotype analysis placed the cataract locus in a 15.3-cM region between markers D16S518 and D16S511 (maximum lod score, 3.612), corresponding 16q23.1.

Through mutation screening of a panel of patients with hereditary congenital cataract, Jamieson et al. (2002) identified a missense mutation in the MAF gene (177075.0001) in affected members of a 3-generation family with autosomal dominant juvenile-onset cataract, some of whom also had microcornea.

In affected members of a 3-generation family with cerulean congenital cataract, some of whom also had microcornea, Vanita et al. (2006) sequenced the MAF gene and identified a heterozygous missense mutation in the MAF gene (177075.0002) that cosegregated with the disease. The mutation was not found in 106 unrelated controls.

In 3 families and 1 sporadic patient with congenital cataract and microcornea, Hansen et al. (2007) analyzed 13 lens-expressed cataract genes and identified heterozygosity for a missense mutation in the MAF gene (R299S; 177075.0003) in 4 affected members of a 3-generation family. The mutation, which segregated with disease in the family, was not found in 152 controls.

In a 3-generation Japanese family with congenital cataract with or without microcornea, Narumi et al. (2014) performed whole-exome sequencing and identified a heterozygous missense mutation in the MAF gene (Q303P; 177075.0004). The mutation, which segregated with disease in the family, was not found in 200 Japanese control alleles or in the NHLBI Exome Sequencing Project database.