X-Linked High Myopia Associated With Cone Dysfunction

Abstract

Bornholm eye disease (BED) consists of X-linked high myopia, high cylinder, optic nerve hypoplasia, reduced electroretinographic flicker with abnormal photopic responses, and deuteranopia. The disease maps to chromosome Xq28 and is the first designated high-grade myopia locus (MYP1). We studied a second family from Minnesota with a similar X-linked phenotype, also of Danish descent. All affected males had protanopia instead of deuteranopia. Methods: X chromosome genotyping, fine-point mapping, and haplotype analysis of the DNA from 22 Minnesota family individuals (8 affected males and 5 carrier females) and 6 members of the original family with BED were performed. Haplotype comparisons and mutation screening of the red-green cone pigment gene array were performed on DNA from both kindreds. Results: Significant maximum logarithm of odds scores of 3.38 and 3.11 at = 0.0 were obtained with polymorphic microsatellite markers DXS8106 and DXYS154, respectively, in the Minnesota family. Haplotype analysis defined an interval of 34.4 cM at chromosome Xq27.3-Xq28. Affected males had a red-green pigment hybrid gene consistent with protanopia. We genotyped Xq27-28 polymorphic markers of the family with BED, and narrowed the critical interval to 6.8 cM. The haplotypes of the affected individuals were different from those of the Minnesota pedigree. Bornholm eye disease-affected individuals showed the presence of a green-red hybrid gene consistent with deuteranopia. Conclusions: Because of the close geographic origin of the 2 families, we expected affected individuals to have the same haplotype in the vicinity of the same mutation. Mapping studies, however, suggested independent mutations of the same gene. The red-green and green-red hybrid genes are common X-linked color vision defects, and thus are unrelated to the high myopia and other eye abnormalities in these 2 families. Clinical Relevance: X-linked high myopia with possible cone dysfunction has been mapped to chromosome Xq28 with intervals of 34.4 and 6.8 centimorgan for 2 families of Danish origin.

CSNB1 in Chinese families associated with novel mutations in NYX

“…Such a finding is present in Caucasian patients with NYX mutation (Jacobi et al 2002;Zeitz et al 2005) as well as patients with other diseases, such as X-linked myopia (Haim et al 1988;Young et al 2004;Zhang et al 2006) and CSNB2 (OMIM 300071). Functional analysis identified that retinal ON-pathway dysfunction is involved in CSNB1, CSNB2 and GRM6 mutations (Dryja et al 2005;Khan et al 2005;Langrova et al 2002).…”

Refinement of the MYP3 locus on human chromosome 12 in a German family with Mendelian autosomal dominant high-grade myopia by SNP array mapping

“…refractive error and propensity to develop further ocular complications, has allowed considerable progress in the study of myopia development. Two X-linked recessive forms of myopia/cone dysfunction and sole myopia have been identified (MYP1, OMIM 310460 and MYP13, OMIM 300613) on chromosome Xq28 (15,16) (23), and at chromosome 10q21.1 (24).…”

“…Based on genetic studies in families and/or unselected single patients with inherited myopia, up to 15 loci responsible for or involved in non-syndromic myopia have been mapped on human chromosomes to date. Despite the considerable number of recognized loci, no disease genes, either for Xchromosomal recessive ('MYP1' OMIM 310460, MYP13 OMIM 300613) (15)(16)(17) or autosomal dominant disease phenotypes (MYP2 OMIM 160700, MYP3 OMIM 603221, MYP4 OMIM 608367, MYP5 OMIM 608474, MYP11 OMIM 609994, MYP12 OMIM 609994, and myopia locating to chromosome 10q21.1) (18)(19)(20)(21)(22)(23)(24) have been identified. This also holds true for the genes involved in common myopia where six independent loci have been determined in the recent past (MYP6 OMIM 608908, MYP7 OMIM 609256, MYP8 OMIM 609257, MYP9 OMIM 609258, MYP10 OMIM 609259, and MYP14 OMIM 610320) (25)(26)(27).…”

Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations

“…[2,3,14] XLCD is a heterogeneous condition characterised by loss of colour vision, impaired visual acuity, macular atrophy and ERG …”

“…[1][2][3][4][5] These allelic X-linked cone opsin disorders display wide inter-and intrafamilial variability. However, in the majority the visual defect is non-progressive.…”