X-Linked High Myopia Associated With Cone Dysfunction | Genetics and Genomics | JAMA Ophthalmology | JAMA Network
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Ophthalmic Molecular Genetics
June 2004

X-Linked High Myopia Associated With Cone Dysfunction

Author Affiliations

From the Departments of Ophthalmology (Drs Young, Ronan, and King andMss Alvear and Holleschau) and Genetics (Drs Young, Dewan, Atwood, Oetting,and King, and Ms Brott), University of Minnesota Medical School, Minneapolis;Division of Ophthalmology, The Children's Hospital of Philadelphia and theUniversity of Pennsylvania, Philadelphia (Dr Young and Mr Scavello and MsPaluru); Departments of Medicine (Medical Genetics) and Genome Sciences, Universityof Washington, Seattle (Drs Deeb, Hayashi, and Motulsky); Department of Ophthalmology,Health Partners Inc, Arden Hills, Minn (Dr Benegas); Section of Clinical Genetics,Department of Pediatrics, University Hospital, Rigshospitalet, Copenhagen,Denmark (Dr Schwartz); and National Eye Clinic for the Visually Impaired,Hellerup, Denmark (Dr Rosenberg). The authors have no relevant financial interestin this article.



Arch Ophthalmol. 2004;122(6):897-908. doi:10.1001/archopht.122.6.897

Objective  Bornholm eye disease (BED) consists of X-linked high myopia, high cylinder,optic nerve hypoplasia, reduced electroretinographic flicker with abnormalphotopic responses, and deuteranopia. The disease maps to chromosome Xq28and is the first designated high-grade myopia locus (MYP1). We studied a second family from Minnesota with a similar X-linkedphenotype, also of Danish descent. All affected males had protanopia insteadof deuteranopia.

Methods  X chromosome genotyping, fine-point mapping, and haplotype analysisof the DNA from 22 Minnesota family individuals (8 affected males and 5 carrierfemales) and 6 members of the original family with BED were performed. Haplotypecomparisons and mutation screening of the red-green cone pigment gene arraywere performed on DNA from both kindreds.

Results  Significant maximum logarithm of odds scores of 3.38 and 3.11 at thetas;= 0.0 were obtained with polymorphic microsatellite markers DXS8106 and DXYS154, respectively, in theMinnesota family. Haplotype analysis defined an interval of 34.4 cM at chromosomeXq27.3-Xq28. Affected males had a red-green pigment hybrid gene consistentwith protanopia. We genotyped Xq27-28 polymorphic markers of the family withBED, and narrowed the critical interval to 6.8 cM. The haplotypes of the affectedindividuals were different from those of the Minnesota pedigree. Bornholmeye disease–affected individuals showed the presence of a green-redhybrid gene consistent with deuteranopia.

Conclusions  Because of the close geographic origin of the 2 families, we expectedaffected individuals to have the same haplotype in the vicinity of the samemutation. Mapping studies, however, suggested independent mutations of thesame gene. The red-green and green-red hybrid genes are common X-linked colorvision defects, and thus are unrelated to the high myopia and other eye abnormalitiesin these 2 families.

Clinical Relevance  X-linked high myopia with possible cone dysfunction has been mappedto chromosome Xq28 with intervals of 34.4 and 6.8 centimorgan for 2 familiesof Danish origin.