Cataract 12, Multiple Types

A number sign (#) is used with this entry because multiple types of cataract are caused by heterozygous mutation in the gene encoding beaded filament structural protein-2 (BFSP2; 603212) on chromosome 3q22.

Description

Mutations in the BFSP2 gene have been found to cause multiple types of cataract, which have been described as juvenile-onset lamellar, cortical, nuclear embryonic; and congenital nuclear, sutural, stellate, Y-sutural, and punctate cortical.

Clinical Features

Kramer et al. (2000) studied 12 affected and 13 unaffected members of a 4-generation family with autosomal dominant congenital cataract. Affected family members had congenital nuclear and sutural cataracts of variable severity, with some family members undergoing surgery in childhood and others never requiring surgery. One 20-year-old female with visual acuities of 20/40 OD and 20/30 OS had striking anterior and posterior sutural opacities with some smaller scattered whitish cortical opacities and radially oriented fine vacuoles. Jakobs et al. (2000) studied this family further and stated that the cataract phenotypes included stellate or spoke-like cortical cataracts, and that the mildest expression of the cataract was that of spoke-like anterior and posterior subcapsular cortical opacities with a ground-glass appearance throughout the cataract and, most notably, the above-mentioned radially oriented fine vacuoles.

Conley et al. (2000) reported a 5-generation family segregating juvenile-onset progressive cataract. Age at onset ranged from 8 years to the late 20s; no individuals were diagnosed with cataracts at birth. The earliest reported findings were a general haze of the lens with prominent sutures, developing into lamellar cataracts in 3 cases, cortical cataract in 3 cases, 'scattered lens opacities' in 1 case, and nuclear embryonic cataract with central snowflake in 1 case. One patient was noted to have optic nerve deformity with bilateral amblyopia. Visual acuity ranged from moderate to severe myopia in 8 of 11 affected individuals in whom measurements were reported; none had 20/20 visual acuity. Conley et al. (2000) stated that the sutural opacities and cortical changes described in the presurgical 20-year-old female by Kramer et al. (2000) were very similar to the cataracts observed in several family members in their study.

Zhang et al. (2004) studied 12 of 15 affected members of a 4-generation Han Chinese family segregating autosomal dominant Y-sutural cataract and myopia. All 12 affected individuals had bilateral isolated Y-shaped sutural cataracts, with the white lens opacity linearly superimposed on the branches of the anterior Y- and posterior inverted Y-sutures, giving a feather-duster appearance to each branch. In a 4-year-old boy, mild opacity of the Y-sutures was the only sign of cataract, with the remainder of the lens clear. Affected children and their parents were generally unaware of visual problems before 7 years of age, at which time they experienced decreased visual acuity, although it was unclear whether this was due to the cataract or the accompanying myopia. The authors noted that the myopia in this family was more likely related to axial length than to lens changes, since ocular axial length was increased in the 5 affected individuals for whom records were available. In addition to the Y-sutural opacity, patients developed slowly progressive punctate cortical opacities around the third decade and later.

Mapping

Kramer et al. (2000) performed linkage analysis in a large 4-generation family segregating autosomal dominant congenital nuclear and sutural cataracts and obtained a maximum multipoint lod score of 6.94 across a 0.4-cM region between markers D3S3674 and D3S3612 on chromosome 3q21-q22.3; the maximum 2-point lod score was obtained at D3S1273 (6.65 at theta = 0).

Conley et al. (2000) performed linkage analysis in 29 members of the 5-generation family with autosomal dominant juvenile-onset cataracts and obtained a maximum 2-point lod score of 3.67 (theta = 0.07) at marker D3S1744 on chromosome 3q21.2-q22.3. Multipoint linkage analysis was suggestive for an estimated 14-cM interval flanked by markers D3S1267 and D3S3612.

Zhang et al. (2004) performed linkage analysis in 12 affected and 12 unaffected members of a 4-generation Han Chinese family with autosomal dominant Y-sutural cataract and myopia and obtained a maximum lod score of 5.72 (theta = 0) at D3S1292; recombination events defined an 11.4-cM (13.5-Mb) region between D2S3606 and D3S1309. Linkage analysis of myopia performed independently of cataract while varying the penetrance and phenocopy rate yielded a maximum lod score of 3.79 at D3S1292 with full penetrance and a 6% phenocopy rate.

Molecular Genetics

In affected members of a 5-generation family with autosomal dominant juvenile-onset cataract, Conley et al. (2000) identified a missense mutation in the BFSP2 gene (R287W; 603212.0001). The mutation was not found in 96 unrelated control individuals; however, 1 unaffected 29-year-old female family member carried the mutation, suggesting that the mutation was not fully penetrant or that the age-at-onset spectrum in this family was quite broad.

In affected members of a 4-generation family with autosomal dominant congenital cataract previously described by Kramer et al. (2000), Jakobs et al. (2000) identified an in-frame deletion in the BFSP2 gene (E233del; 603212.0002).

In 12 affected individuals of a 4-generation Han Chinese pedigree with Y-sutural cataract and myopia mapping to 3q22, Zhang et al. (2004) identified heterozygosity for the E233del mutation in the BFSP2 gene. The mutation was not found in 12 unaffected members of the family or in 384 unrelated Han Chinese control chromosomes.