Cataract 31, Multiple Types

A number sign (#) is used with this entry because of evidence that multiple types of cataract are caused by heterozygous mutation in the CHMP4B gene (610897) on chromosome 20q11.

Description

Mutations in the CHMP4B gene have been found to cause multiple types of cataract, which have been described as posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular.

The preferred title/symbol of this entry was formerly 'Cataract, Posterior Polar, 3; CTPP3.'

Clinical Features

Yamada et al. (2000) described a Japanese family in which 10 members in 4 generations were affected with autosomal dominant posterior polar cataract. The cataract was characterized by progressive, disc-shaped, posterior subcapsular opacity.

Shiels et al. (2007) reported 15 affected individuals in a large 6-generation Caucasian family with progressive childhood posterior subcapsular cataracts. Cataracts progressed with age to affect the nucleus and anterior subcapsular regions of the lens. Age at diagnosis varied from 4 to 20 years.

Mapping

By linkage analysis of the Japanese family with cataract described by Yamada et al. (2000), Yamada et al. (2000) assigned the locus, which they designated CPP3, to chromosome 20p12-q12.

Shiels et al. (2007) performed linkage analysis in a large 6-generation Caucasian family with autosomal dominant progressive childhood posterior subcapsular cataract and, after excluding known autosomal dominant cataract loci, found significant linkage on chromosome 20q with a maximum 2-point lod score of 5.50 at D20S847. Analysis of recombinant events in affected individuals followed by genotyping with biallelic SNP markers narrowed the region of interest to a 0.9-Mb interval containing approximately 80 genes, none of which were obvious functional candidates for cataracts.

Molecular Genetics

In a large 6-generation Caucasian family with autosomal dominant progressive childhood posterior subcapsular cataract mapping to chromosome 20q, Shiels et al. (2007) sequenced positional candidate genes and identified a heterozygous mutation in the CHMP4B gene (D129V; 610897.0001) that cosegregated with disease and was not found in 384 control chromosomes. The mutation was not found in unaffected family members except for a 17-year-old male who was believed to be either nonpenetrant or presymptomatic. Shiels et al. (2007) also identified a heterozygous mutation (E161K; 610897.0002) in the CHMP4B gene in affected individuals of the Japanese family previously reported by Yamada et al. (2000) and Yamada et al. (2000).

Exclusion Studies

In a Japanese family with cataract mapping to chromosome 20p12-q12, Yamada et al. (2000) performed sequence analysis on the entire coding region of the BFSP1 gene (603307), but found no base substitutions or deletions.