Objective: Pathological myopia has a genetic background. Previous studies have mapped six loci at 18p11.31, 12q21-23, 7q36, 17q21-22, 4q22-q27 and 2q37.1 in autosomal dominant (AD) pathological myopia. The aim of the present study was to map the mutate gene associated with this disorder in Chinese population.
Methods: A family with AD pathological myopia including 12 individuals, of which 7 members were affected, consented to participate our study. Three hundred and thirty pairs of highly heterozygous microsatellite marker primers were selected for a genome-wide screening. Two-point linkage was calculated by LINKAGE package in an autosomal dominant mode with full penetrance at gene frequency of 0.0133. Multipoint LOD scores were calcu1ated by use of GENEHUNTER program. Genetic distance between marker loci examined was determined on the basis of Genethon linkage map. Haplotype analysis was performed by software of Cyrillic 2.0 based on the lowest recombination principle.
Results: Evidence of significant linkage was found on chromosome 15q in the family by two-point linkage analysis. The maximum LOD score was 1.76 with the markers D15S1010, D15S1007 and D15S1042 at a recombination fraction of 0.00. Multipoint linkage analysis also supported existence of linkage on this region with NPL score 5.16. Haplotype analysis refined this myopia locus to a 12 cM interval between D15S1019 and D15S146 on 15q12 - 13. No evidence of linkage was found at any known myopia loci, including AD pathological myopia loci on 18p11.31, 12q21 - 23, 7q36, 17q21 - 22, 4q22 - q27 and 2q37.1, and syndromic myopia loci on 15q15-21, 12q13.11-13.2, 6p21.3, 1q21-31, 1p21 and 21q22.3.
Conclusions: Our study indicates a novel myopia locus on 15q12 - 13. There are 94 known genes locate on this region, screening for sequence of candidate genes within this region will be helpful to find the mutant gene. This study also provides additional support for genetic heterogeneity of this disorder.