Cataract 41

A number sign (#) is used with this entry because of evidence that congenital nuclear cataract-41 (CTRCT41) is caused by heterozygous mutation in the WFS1 gene (606201) on chromosome 4p16. One such family has been reported.


Cataract is an opacification of the lens or lens capsule in the eye and is the most common cause of childhood blindness in the world, with an incidence of 1 to 3 per 10,000 live births. If untreated in infancy or childhood, it frequently causes visual impairment and can result in irreversible amblyopia. Nuclear cataract refers to opacification within the embryonal and/or fetal nuclei of the lens (summary by Berry et al., 2013).


In a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract without other ocular or systemic features, Berry et al. (2013) performed genotyping with SNP and microsatellite markers and identified a candidate interval on chromosome 4p16, obtaining a 2-point lod score of 2.62 with marker D4S432 (theta = 0). Recombination events narrowed the interval to a 6.6-Mb region at 4p16.1.


Reese et al. (1987) described congenital cataract in father and infant son, both of whom had translocation t(3;4)(p26.2;p15). In the child, the cataracts were not found by an examining physician at age 4 weeks, but 'milky' pupils were noted by the mother at 7 weeks, and at 9 weeks both lenses showed fully mature cataracts with no retinal reflex. The father had dense bilateral cataracts diagnosed at birth and underwent uneventful lens aspirations at 3 and 8 months of age; thus, it is possible that the cause of this cataract is a genetic change at or near one of the breakpoints, 3p26.2 or 4p15.

Molecular Genetics

In a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract mapping to chromosome 4p16.1, Berry et al. (2013) sequenced 13 positional candidate genes but found no mutations. Exome sequencing in an affected family member identified a heterozygous missense mutation in the WFS1 gene (E462G; 606201.0023), and direct genomic sequencing confirmed that the mutation cosegregated completely with disease in the family. Screening of the WFS1 gene in a panel of 50 unrelated individuals with autosomal dominant cataract did not reveal any other mutations.