Cataract 18

A number sign (#) is used with this entry because of evidence that cataract-18 (CTRCT18) is caused by homozygous mutation in the FYCO1 gene (607182) on chromosome 3p21.3.

Description

Mutations in the FYCO1 gene have been identified in families with autosomal recessive cataract described as congenital and congenital nuclear.

The preferred title/symbol of this entry was formerly 'Cataract, Autosomal Recessive Congenital 2; CATC2.'

Clinical Features

Chen et al. (2011) studied 12 consanguineous Pakistani families segregating autosomal recessive congenital cataract. All affected individuals available for examination had bilateral nuclear cataracts that were either present at birth or developed in infancy. No other ocular or systemic abnormalities were present in these families.

Mapping

Pras et al. (2001) mapped a locus for autosomal recessive cataract to chromosome 3p in 3 inbred Arab families. All affected individuals had been diagnosed with cataract within a few weeks after birth, and operated upon during the first 3 months of life. The parents of the affected sibs were first cousins in all 3 families. One of the families had been reported by Pras et al. (2000). A SNP-based genomewide search was performed on a pooled DNA sample from 6 affected family members in a search for regions showing homozygosity. Using conventional microsatellite markers, regions of homozygosity were further analyzed in all families. A region on chromosome 3p spanning 43 Mb showed homozygosity with 13 consecutive SNPs. Three microsatellite markers from this region yielded lod scores greater than 3.00. A maximal 2-point lod of 4.83 was obtained with the marker D3S1298 at theta = 0.004. Haplotype analysis placed the disease gene in a 20-Mb interval between D3S1768 and D3S2409.

In 8 unrelated consanguineous Pakistani families segregating autosomal recessive congenital cataract, Chen et al. (2011) performed genomewide linkage analysis and fine mapping and found significant or suggestive linkage to chromosome 3p22-p21. Chen et al. (2011) noted that the 3.5-cM (12-Mb) linked region, flanked by D3S3685 and D3S1289, overlapped the CATC2 locus previously described by Pras et al. (2001).

Molecular Genetics

In affected members of a consanguineous Pakistani family segregating autosomal recessive congenital cataract (arCC) that mapped to chromosome 3p22-p21, Chen et al. (2011) analyzed 35 candidate genes and identified homozygosity for a nonsense mutation in the FYCO1 gene (607182.0001); analysis of FYCO1 in 7 additional Pakistani families with arCC mapping to 3p22-p21 revealed homozygosity for 5 different mutations in FYCO1 (see, e.g., 607182.0002 and 607182.0004-607182.0005). Chen et al. (2011) also sequenced FYC01 in 1 affected individual from each of 63 Pakistani families with arCC that did not obtain a lod score greater than 3 at 3p22-p21 and identified homozygous mutations in 4 of the probands (see, e.g., 607182.0003-607182.0005). The mutations segregated with disease in all of the families and were not found in 300 unrelated ethnically matched control chromosomes. In addition, homozygosity for a nonsense mutation in FYC01 was identified in an affected member of a consanguineous Arab Israeli family with congenital cataracts originally reported by Pras et al. (2001) ('family 1'; 607182.0006). Chen et al. (2011) stated that the 43 mutation-positive Pakistani patients represented approximately 10% of the total genetic load of cataracts in their ongoing collaborative study of arCC in Pakistan involving 125 families, suggesting that FYCO1 mutations are among the most common causes of inherited congenital cataracts in the Pakistani population as a whole.