TY - JOUR
T1 - Congenital motor nystagmus linked to Xq26-q27
AU - Kerrison, John B.
AU - Vagefi, M. Reza
AU - Barmada, M. Michael
AU - Maumenee, Irene H.
N1 - Funding Information:
We would like to thank all family members who participated. Thanks to Olof Sundin for his useful guidance. This study was supported in part by a grant from the Knights Templar Eye Foundation (to J.B.K.), by a grant from Research to Prevent Blindness, New York, and by the Krieble and Walter Edel Funds of the Johns Hopkins Center for Hereditary Eye Diseases (to I.H.M.).
PY - 1999
Y1 - 1999
N2 - Congenital motor nystagmus (CMN) is a hereditary disorder characterized by bilateral ocular oscillations that begin in the first 6 mo of life. It must be distinguished from those genetic disorders - such as ocular albinism (OA), congenital stationary night blindness (CSNB), and blue-cone monochromatism (BCM) - in which nystagmus accompanies a clinically apparent defect in the visual sensory system. Although CMN is presumed to arise from a neurological abnormality of fixation, it is not known whether the molecular defect is located in the eye or in the brain. It may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Three families with CMN inherited in an X-linked, irregularly dominant pattern were investigated with linkage and candidate gene analysis. The penetrance among obligate female carriers was 54%. Evaluation of markers in the region of the genes for X-linked OA, CSNB, and BCM revealed no evidence of linkage, supporting the hypothesis that CMN represents a distinct entity. The gene was mapped to chromosome Xq26-q27 with the following markers: GATA172D05 (LOD score 3.164; recombination fraction [θ] = 0.156), DXS1047 (LOD score 10.296; θ = O), DXS1192 (LOD score 8.174; θ = 0.027), DXS1232 (LOD score 6.015; θ = 0.036), DXS984 (LOD score 6.695; θ = 0), and GATA31E08 (LOD score 4.940; θ = 0.083). Assessment of haplotypes and multipoint linkage analysis, which gave a maximum LOD score of 10.790 with the 1-LOD-unit support interval spanning ∼7 cM, place the gene in a region between GATA172D05 and DXS1192. Evaluation of candidate genes CDR1 and SOX3 did not reveal mutations in affected male subjects.
AB - Congenital motor nystagmus (CMN) is a hereditary disorder characterized by bilateral ocular oscillations that begin in the first 6 mo of life. It must be distinguished from those genetic disorders - such as ocular albinism (OA), congenital stationary night blindness (CSNB), and blue-cone monochromatism (BCM) - in which nystagmus accompanies a clinically apparent defect in the visual sensory system. Although CMN is presumed to arise from a neurological abnormality of fixation, it is not known whether the molecular defect is located in the eye or in the brain. It may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Three families with CMN inherited in an X-linked, irregularly dominant pattern were investigated with linkage and candidate gene analysis. The penetrance among obligate female carriers was 54%. Evaluation of markers in the region of the genes for X-linked OA, CSNB, and BCM revealed no evidence of linkage, supporting the hypothesis that CMN represents a distinct entity. The gene was mapped to chromosome Xq26-q27 with the following markers: GATA172D05 (LOD score 3.164; recombination fraction [θ] = 0.156), DXS1047 (LOD score 10.296; θ = O), DXS1192 (LOD score 8.174; θ = 0.027), DXS1232 (LOD score 6.015; θ = 0.036), DXS984 (LOD score 6.695; θ = 0), and GATA31E08 (LOD score 4.940; θ = 0.083). Assessment of haplotypes and multipoint linkage analysis, which gave a maximum LOD score of 10.790 with the 1-LOD-unit support interval spanning ∼7 cM, place the gene in a region between GATA172D05 and DXS1192. Evaluation of candidate genes CDR1 and SOX3 did not reveal mutations in affected male subjects.
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U2 - 10.1086/302244
DO - 10.1086/302244
M3 - Article
C2 - 9973299
AN - SCOPUS:0033070051
SN - 0002-9297
VL - 64
SP - 600
EP - 607
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -