Mi. Othman et al., AUTOSOMAL-DOMINANT NANOPHTHALMOS (NNO1) WITH HIGH HYPEROPIA AND ANGLE-CLOSURE GLAUCOMA MAPS TO CHROMOSOME-11, American journal of human genetics, 63(5), 1998, pp. 1411-1418
Nanophthalmos is an uncommon developmental ocular disorder characteriz
ed by a small eye, as indicated by short axial length, high hyperopia
(severe farsightedness), high lens/eye volume ratio, and a high incide
nce of angle-closure glaucoma. We performed clinical and genetic evalu
ations of members of a large family in which nanophthalmos is transmit
ted in an autosomal dominant manner. Ocular examinations of 22 affecte
d 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; me
an 18.13 mm). Twelve affected family members had angle-closure glaucom
a or occludable anterior-chamber angles. Linkage analysis of a genome
scan demonstrated highly significant evidence that nanophthalmos in th
is 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 re
combination fraction of .00 for marker D11S903 and a multipoint maximu
m LOD score of 6.31 for marker D11S1313. NNO1 is the first human locus
associated with nanophthalmos or with an angle-closure glaucoma pheno
type, and the identification of the NNO1 locus is the first step towar
d the cloning of the gene. A cloned copy of the gene will enable exami
nation of the relationship, if any, between nanophthalmos and less sev
ere farms of hyperopia and between nanophthalmos and other conditions
in which angle-closure glaucoma is a feature.