Autosomal dominant nanophthalmos (NNO1) with high hyperopia and angle-closure glaucoma maps to chromosome 11.
Nanophthalmos is an uncommon developmental ocular disorder characterized by a small eye, as indicated by short axial length, high hyperopia (severe farsightedness), high lens/eye volume ratio, and a high incidence of angle-closure glaucoma. We performed clinical and genetic evaluations of members of a large family in which nanophthalmos is transmitted in an autosomal dominant manner. Ocular examinations of 22 affected family members revealed high hyperopia (range +7.25-+13.00 diopters; mean +9.88 diopters) and short axial length (range 17.55-19.28 mm; mean 18.13 mm). Twelve affected family members had angle-closure glaucoma or occludable anterior-chamber angles. Linkage analysis of a genome scan demonstrated highly significant evidence that nanophthalmos in this family is the result of a defect in a previously unidentified locus (NNO1) on chromosome 11. The gene was localized to a 14.7-cM interval between D11S905 and D11S987, with a maximum LOD score of 5. 92 at a recombination fraction of .00 for marker D11S903 and a multipoint maximum LOD score of 6.31 for marker D11S1313. NNO1 is the first human locus associated with nanophthalmos or with an angle-closure glaucoma phenotype, and the identification of the NNO1 locus is the first step toward the cloning of the gene. A cloned copy of the gene will enable examination of the relationship, if any, between nanophthalmos and less severe forms of hyperopia and between nanophthalmos and other conditions in which angle-closure glaucoma is a feature.
Othman
M I
MI
Department of Opthalmology, University of Michigan, Ann Arbor, MI, USA.
Sullivan
S A
SA
Skuta
G L
GL
Cockrell
D A
DA
Stringham
H M
HM
Downs
C A
CA
Fornés
A
A
Mick
A
A
Boehnke
M
M
Vollrath
D
D
Richards
J E
JE
D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D015812:Glaucoma, Angle-Closure / Q000235:genetics*; D006801:Humans; D006956:Hyperopia / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010375:Pedigree; D018454:Spouses
D005819:Genetic Markers