Cataract 15, Multiple Types

A number sign (#) is used with this entry because of evidence that multiple types of cataract (CTRCT15) are caused by heterozygous mutation in the MIP gene (154050) on chromosome 12q13.

Description

Mutations in the MIP gene have been found to cause multiple types of cataract, which have been described as 'polymorphic,' progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical.

Clinical Features

Berry et al. (2000) reported a 4-generation pedigree segregating autosomal dominant cataract. All affected individuals had discrete, congenital, isolated, progressive, bilateral, punctate lens opacities limited to mid- and peripheral lamellae; some individuals had asymmetric anterior and posterior polar opacification, and one individual had predominantly cortical cataract, thus prompting Berry et al. (2000) to describe the cataract as polymorphic.

Bateman et al. (1986) and Bateman et al. (2000) studied a 4-generation American family of European descent (family ADC2) segregating autosomal dominant congenital cataracts described as embryonal nuclear or pulverulent cortical. The cataracts were sometimes asymmetric. Geyer et al. (2006) studied 12 members of family ADC2; 10 exhibited variable expressivity of cataract with radiating, vacuolar, or dense opacities in the embryonal nucleus, and 2 had milder cataracts with fine punctate cortical opacities.

Mapping

Berry et al. (2000) performed linkage analysis on a 4-generation family segregating autosomal dominant cataract. After excluding a number of candidate loci, they obtained positive 2-point lod scores at marker D12S1676 (Z = 3.91 at theta = 0) spanning the MIP locus on chromosome 12q.

In the family segregating autosomal dominant cataract reported by Bateman et al. (1986), in which previously identified cataract loci had been excluded, Bateman et al. (2000) found linkage to chromosome 12, with a maximum lod score of 4.62 with marker D12S90.

Molecular Genetics

In affected members of a 4-generation pedigree segregating autosomal dominant cataract mapping to chromosome 12q, Berry et al. (2000) identified a heterozygous missense mutation in the MIP gene (T138R; 154050.0001). In an unrelated family with autosomal dominant cataract with sutural opacities, they identified a different heterozygous missense mutation in the MIP gene (E134G; 154050.0002).

In affected members of a family segregating autosomal dominant cataract, originally reported by Bateman et al. (1986), Geyer et al. (2006) identified a frameshift mutation in the MIP gene (3223delG; 154050.0003). The mutation was not found in 11 unaffected family members tested.