A progressive autosomal recessive cataract locus maps to chromosome 9q13-q22

Abstract

Cataracts are the leading cause of blindness in most countries. Although most hereditary cases appear to follow an autosomal dominant pattern of inheritance, autosomal recessive inheritance has been clearly documented and is probably underrecognized. We studied a large family-from a relatively isolated geographic region-whose members were affected by autosomal recessive adult-onset pulverulent cataracts. We mapped the disease locus to a 14-cM interval at a novel disease locus, 9q13-q22 (between markers D9S1123 and D9S257), with a LOD score of 4.7. The study of this progressive and age-related cataract phenotype may provide insight into the cause of the more common sporadic form of age-related cataracts.

Figure 1

Genealogy and summarized haplotype showing the most informative markers. All spouses were examined and found to be normal. Blackened symbols indicate clinically affected individuals; unblackened symbols represent unaffected relatives. Unblackened symbols containing an “N” indicate relatives ⩾30 years old who were examined but who did not show signs of the disease; empty unblackened symbols indicate unaffected relatives who are ⩽30 years old; slashes indicate deceased individuals. The hatched boxes indicate the affected haplotype, whereas the unhatched boxes indicate the unaffected haplotype. “XX” indicates the beginning and end of the disease-gene interval. “?” indicates the genotype was not available.

Figure 2

Drawing of the ARPC lens opacity. Top, Individual III:15, at age 20 years, showing pulverulent lamellar and cortical opacity. Bottom, Individual III:5, at age 47 years, showing additional nuclear and posterior subcapsular changes.

Figure 3

SIMWALK2 analysis of markers at the 9q13-q22 locus. Simulated location scores for ARPC vs. chromosome 9 markers. The maximum log₁₀ location score was 4.7, with D9S768. The 14-cM disease interval, as defined by haplotype analysis, was between D9S1123 and D9S257.