A New Suceptibility Locus of Familial High Myopia on Chromosome 7p15.3

Abstract

Abstract: : Purpose: Familial non syndromic high myopia (MYP) is characterized by a refraction defect greater than –6 D. MYP is one of the major causes of legal blindness in industrialized countries. It is assumed that the trait is often autosomal dominant which does not exclude a rarer X–linked transmission nor more complex mode(s) of inheritance. To date at least 6 different loci are involved in MYP susceptibility on chromosome Xq28 (MYP1), 18p11.31 (MYP2), 12q21 (MYP3), 7q36 (MYP4), 17q21–22, 11p13.3. The aim of this work is to localize and identify gene(s) involved in MYP. Methods: A 10 cM wide genome scan was performed in 50 french families that each included at least 2 myopic subjects with refraction higher than –6 D, in two or more generations. A total of 340 subjects including 135 high myopic were genotyped. Linkage analysis was conducted with the Genehunter software using parameters previously computed in 32 French MYP families^a and the non–parametric option. Genetic heterogeneity in the whole population was tested using the H–lod function. Further refinement was performed in the regions whose lod–scores were > 1.5. Results: Genetic heterogeneity was evidenced in the french population. 4 families were found linked to the previously described MYP2 locus (parametric multipoint lod–score = 2.53), 10 families to MYP4 (multi–point lod–score = 5.50 and two–point lod–score of 3.50 at &#952 = 0 for the marker D7s2465). Finally evidence of a significant linkage was found in 12 families on a new locus on chromosome 7p15.3. The non–parametric multipoint lod–score was 3.71 within a region of approximately 10 cM between marker D7S507 and marker D7S529. The parametric multipoint lod–score was 4.02. The maximum two–point lod–score was 2.80 at &#952 = 0 with marker D7S673. Conclusions: This study allowed the identification of a new locus for MYP in French families increasing the notion of the genetic heterogenity of the disorder. The region harbouring marker D7S673 which is located in a serine–threonine kinase putative gene whose involvement in MYP remains to be demonstrated. ^a Naiglin et al. Ann. Génét. 1999 ;42 :140–6.

Keywords: gene mapping • myopia