Cataract 23, Multiple Types

A number sign (#) is used with this entry because cataract-23 (CTRCT23) is caused by heterozygous mutation in the crystallin beta-A4 gene (CRYBA4; 123631) on chromosome 22q12.

Description

Mutation in the CRYBA4 gene has been found in families with cataract described as congenital, lamellar, and nuclear.

Clinical Features

Santhiya et al. (2004) reported a 4-generation Indian family with autosomal dominant congenital lamellar cataract. Billingsley et al. (2006) examined 13 affected and several unaffected individuals from this family. Most affected individuals had been diagnosed during childhood; however, 2 affected individuals had not yet had cataracts removed, suggesting early insult with variable expressivity.

Billingsley et al. (2006) reported a patient with bilateral microphthalmia and cataracts with secondary enophthalmia (sinking of the eyes) identified in a series of 32 patients with bilateral microphthalmia.

Zhou et al. (2010) reported a 3-generation Chinese family in which a father and son had congenital nuclear cataract with microcornea. Both showed symptoms of vision decrease before 2 years of age.

Molecular Genetics

In the Indian family with autosomal dominant congenital lamellar cataract originally reported by Santhiya et al. (2004), Billingsley et al. (2006) detected a heterozygous missense mutation in the CRYBA4 gene (F94S; 123631.0001).

In a patient with bilateral microphthalmia and cataracts, Billingsley et al. (2006) detected a heterozygous mutation in exon 4 of the CRYBA4 gene (L69P; 123631.0002). Protein structure modeling predicted that the L69P change, in the middle of the CRYBA4 beta-sheet, would likely break the beta-sheet. The mutant structure would be very unstable and would not fold properly. Billingsley et al. (2006) sought mutations in the CRYBA4 gene in microphthalmia based on the demonstration of CRYBB2 involvement in microphthalmia and cataract (see 601547) and the interaction of CRYBB2-CRYBA4 monomers.

In a Chinese father and son with congenital nuclear cataract and microcornea, Zhou et al. (2010) identified a heterozygous mutation in the CRYBA4 gene (G64W; 123631.0003) that segregated with the disease in the family.