Cataract 17, Multiple Types

A number sign (#) is used with this entry because multiple types of cataract with or without microcornea (CTRCT17) are caused by heterozygous or homozygous mutation in the beta-B1 crystallin gene (CRYBB1; 600929) on chromosome 22q12.

Description

Mutations in the CRYBB1 gene have been found to cause multiple types of cataract, which have been described as congenital nuclear, congenital nuclear with anterior and posterior Y-suture and polar opacities, and pulverulent.

The preferred title/symbol for this entry was formerly 'Cataract, Congenital Nuclear, Autosomal Recessive 3; CATCN3.'

Clinical Features

Mackay et al. (2002) studied 8 affected members in 4 generations of a family segregating autosomal dominant pulverulent cataract. The cataract was bilateral in all cases and consisted of fine, dust-like opacities that affected mainly the central zone, or fetal nucleus, of the lens but also affected the cortex and the anterior and posterior Y-suture regions. Opacities were present from birth. There was no family history of other ocular or systemic abnormalities.

Willoughby et al. (2005) reported a large 3-generation family from the UK segregating autosomal dominant congenital cataract and microcornea. All 11 affected individuals had congenital cataracts, and microcornea was present in 8 of the 10 patients for whom measurements were available. The morphology of the cataract was assessed in 1 patient at birth and showed a dense nuclear cataract with cortical fibers (riders) and anterior and posterior pole opacities. The majority of affected individuals had undergone surgery in infancy, but similar morphology was reported to have been present at birth in all affected family members.

Cohen et al. (2007) studied 2 extended unrelated consanguineous inbred Bedouin families from southern Israel presenting with autosomal recessive congenital nuclear cataract.

Wang et al. (2011) reported a 5-generation Chinese family segregating autosomal dominant congenital cataract and microcornea. Affected individuals presented with bilateral dense nuclear opacities involving the embryonic and fetal nucleus of the lens and an average corneal diameter of 10.4 mm. Cataract features were asymmetric in the 2 eyes of some patients; for example, 1 individual had dense round nuclear opacities in the left eye, whereas the other eye showed irregular nuclear opacities that extended from the nucleus to the peripheral cortex, in the shape of a tortoise. All affected individuals showed cataract within the first year of life and had similar poor vision, ranging from 20/100 to 20/400. Nystagmus and amblyopia were also present.

Inheritance

The mode of inheritance of CTRCT17 is autosomal dominant in some families (see, e.g., Mackay et al., 2002) and autosomal recessive in others (see Cohen et al., 2007).

Mapping

In a family with autosomal dominant pulverulent cataract, Mackay et al. (2002) found that the disorder mapped to the beta-crystallin gene cluster on 22q11.2.

In 2 unrelated consanguineous inbred Bedouin families segregating congenital nuclear cataract, Cohen et al. (2007) identified a locus on chromosome 22 surrounding marker D22S1156 that demonstrated homozygosity only in affected individuals (lod score greater than 6.57 at theta = 0 for D22S1156).

Molecular Genetics

In affected members of a family segregating autosomal dominant pulverulent cataract, Mackay et al. (2002) identified heterozygosity for a nonsense mutation in the CRYBB1 gene (G220X; 600929.0001).

In a large 3-generation family from the UK with autosomal dominant congenital cataract and microcornea mapping to chromosome 22q11.2-q12.2, Willoughby et al. (2005) sequenced the CRYBB1 gene and identified heterozygosity for an X253R substitution (600929.0003) that segregated fully with disease and was not found in 109 ethnically matched controls. The mutation was not detected in 50 additional patients with congenital cataracts or in 50 patients with age-related cataracts.

In affected members of 2 unrelated consanguineous Bedouin families segregating congenital nuclear cataract, Cohen et al. (2007) identified the same homozygous mutation in exon 2 of the CRYBB1 gene (168delG; 600929.0002). The parents of those affected were heterozygous for the mutation, which was not found in 100 Bedouin control individuals.

In a 5-generation Chinese family with autosomal dominant congenital cataract and microcornea mapping to 22q11.2-q12.1, Wang et al. (2011) analyzed the 4 beta-crystallin genes clustered in that region and identified a missense mutation in the CRYBB1 gene (S129R; 600929.0004) that segregated fully with disease in the family and was not found in 100 controls.