Investigation of Candidate Loci for Familial Nonsyndromic Human Strabismus

Abstract

Abstract: : Purpose: Strabismus (squint) is a misalignment of the visual axes affecting approximately 2–5% of the population. Twin and family studies suggest a substantial genetic component, especially for esotropia (an inward deviation) in Caucasians. However the association of strabismus with a variety of chromosomal abnormalities and with prematurity and birth trauma suggests genetic complexity and an environmental component to causation. To date no genes have been implicated in concomitant strabismus, but one susceptibility locus, STBMS1, on chromosome 7p22, has been described. Methods: We have ascertained over 100 families with two or more individuals affected by esotropia and/or hyperopia (greater than or equal to +1.50D). Thus far we have sampled a panel of 74 Caucasian individuals from 10 pedigrees, including 4 larger families. In this panel we carried out a preliminary linkage screen of several candidate loci. Markers were tested covering the STBMS1 locus, the whole of chromosome 21 and loci on chromosomes 8p21 and 15q26. Chromosome 21 markers were tested since Downs syndrome children have a higher incidence of esotropia with an accommodative element, compared to those children with strabismus associated with other syndromes. 8p21 and 15q26 markers were tested because of an observation of two siblings with esotropia carrying a balanced 8p:15q translocation. Results: Two of the larger families reveal a pattern of inheritance consistent with linkage to the susceptibility locus, STBMS1, but a third appears unlinked. None of the other markers tested show any evidence of linkage. Conclusions: These data confirm the existence of a susceptibility locus for esotropia in association with hyperopia on chromosome 7p and give further evidence of genetic heterogeneity.

Keywords: strabismus • gene mapping • linkage analysis