Linkage analysis of familial "pathologic" myopia

Purpose. Myopia is a complex disorder likely due to both genetic and environmental influences. Pathologic myopia, defined as myopia greater than -6.00 diopters, shows autosomal dominant inheritance in some families suggesting the existence of one or more responsible genes. The purpose of the current study is to map the gene(s) responsible for familial high myopia. Methods. Eleven families with at least two individuals with -6.00 diopters or higher degrees of myopia were ascertained. These families contained 263 individuals and DNA was available for 117 (68 affected). The average age of diagnosis of myopia was 6.8 years (Range of 1.5-9.5). Linkage analysis using microsatellite markers distributed at a distance of 20-25 cM across the genome was performed using PCR and fluorescent DNA detection. Candidate gene markers intragenic to the identified genes for the Stickler's syndrome (12ql3.1-ql3.3 and 6p21.3), Marian's syndrome (15q21.l), and to the juvenile glaucoma locus on chromosome Iq21-q31 were also analyzed to exclude these potentially confounding disorders. Lod scores were calculated using the MLINK. feature of the computer program FASTLINK. Results. To date, a total of 115 markers have been analyzed, representing 62% of the total genome. Preliminary linkage analysis generated a cumulative lod score of 2.10at athetaof 0.2 with an anonymous marker at 18p. Linkage was excluded from the Stickler's and Marfan's syndromes, and the juvenile glaucoma loci. Conclusion. A genome screen is in progress to map the location of the gene(s) associated with familial high myopia. Preliminary evidence suggests a region on 18p may be involved with myopia. Linkage to additional markers in this region and multipoint analysis will be presented.