A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36.

High myopia often appears as a familial disease. It is usually defined as a refraction error equal to or below −6 diopters (D) in each eye. Highly myopic patients represent 27-33% of the myopic population. The prevalence of the disease in the general population varies according to the country, from 2.1% in the USA, to 3.2% in France, and up to 9.6% in Spain. High myopia is also termed “pathological” myopia because of its potential complications. The highly myopic eye is usually characterised by an abnormal lengthening and a posterior staphyloma. It is often accompanied by glaucoma, cataracts, macular degeneration, and retinal detachment, leading to blindness when the damage to the retina is extremely severe. Both genetic and environmental factors, such as close work, are known to play a role in the aetiology of high myopia. The inheritance of the disease is equivocal. Several genealogical studies have shown autosomal dominant or autosomal recessive modes of inheritance. 5 Rare cases of sex linked transmission have been observed. In a previous study, we showed that, assuming a single gene model, autosomal dominant transmission with weak penetrance was largely present in the families that we studied. Young et al have recently reported linkage of familial high myopia to chromosome regions 18p and 12q. We previously found no evidence for linkage to the former chromosomal region in the families of our study. Several putative candidate loci were excluded as well in these families, such as the locus for Stickler syndrome types 1 and 2, versican and aggregan genes, Marfan 1 syndrome, and a Marfan-like disorder localised to 3p24.2-p25. In order to find new loci implicated in high myopia, we conducted a genome screen in 23 families following an autosomal dominant mode of inheritance with weak penetrance. Here, we provide further evidence for genetic heterogeneity by excluding the chromosome 12q and 18p regions, previously linked to familial high myopia, 9 and report suggestive evidence for the presence of a third autosomal locus on chromosome 7q. SUBJECTS, MATERIALS, AND METHODS Subjects Medical history and ophthalmic assessment were obtained from 140 participants from 21 French families and two Algerian families, after informed consent according to French law. We focused our study on isolated bilateral high myopia. Families with unilateral high myopia, syndromes with high myopia, and myopia of prematurity were excluded. For each patient, subjective refraction and keratometry were performed. Axial lengths were also measured for almost all of the subjects. Objective refraction was measured by automatic refractometry. The refraction defect in spherical equivalent was the criterion chosen to classify subjects into two groups, high myopes and unaffected persons. A subject was considered to be highly myopic if the refraction error in the lesser affected eye was −6 D or below. We considered low myopes (myopia between −6 and −1 D), emmetropes (refraction status between −1 and 1 D), and patients with hyperopia (refraction status greater than 1 D) as unaffected subjects. Details of refractive status are summarised in table 1.