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Cataracts, CRYAA Mutations

OMIM ID:

autosomal recessive
autosomal dominant

Cataracts, CRYAA Mutations

Alternate Names

zonular central nuclear cataract
crystallin alpha-1
CRYAA
autosomal recessive congenital cataract 1
CATC1
autosomal dominant nuclear cataract
autosomal dominant nuclear with iris coloboma
autosomal dominant cataract with microcornea

Defective Genes

CRYAA

Clinical Characteristics

Ocular Features

This seems to be a clinically heterogeneous group of lens opacities all due to mutations in the crystallin gene CRYAA.  Some patients also have colobomas and may have microcornea and corneal opacities.  The lens opacities are usually bilateral but there is considerable asymmetry in their morphology.  Opacities may be nuclear, polar, cortical, sutural, embryonal, and anterior subcapsular in location.  The cataracts are often present at birth.

Systemic Features

Systemic disease is absent.

Genetics

Inheritance

A variety of mutations in the CRYAA (21q22.3) have been reported in a several ethnic groups.  Most pedigrees are consistent with autosomal dominant inheritance but autosomal recessive inheritance has been suggested in other families.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

Lens extraction may be necessary.

Selected Resources

Web Resources

Publications

Displaying 1 - 3 of 3

A novel 3-base pair deletion of the CRYAA gene identified in a large Chinese pedigree featuring autosomal dominant congenital perinuclear cataract

PubMedID: 25729975

A novel mutation in CRYAA is associated with autosomal dominant suture cataracts in a Chinese family

PubMedID: 23288997

Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA)

PubMedID: 18302245