Congenital Motor Nystagmus Linked to Xq26-q27

Abstract

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 [theta] = 0.156), DXS1047 (LOD score 10.296; theta = 0), DXS1192 (LOD score 8.174; theta = 0.027), DXS1232 (LOD score 6.015; theta = 0.036), DXS984 (LOD score 6.695; theta = 0), and GATA31E08 (LOD score 4.940; theta = 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 approximately 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.

Linkage analysis of two families with X-linked recessive congenital motor nystagmus

“…3 Diagram of the X chromosome showing the critical region for X-linked CMN. A, B, C Critical regions for X-linked dominant CMN reported by Kerrison et al (1999Kerrison et al ( , 2001 and Zhang et al (2005), respectively; D linked region for X-linked recessive CMN in this study here mapped to Xq23-q27, which harbors the X-linked dominant CMN locus (Fig. 3).…”

“…Several candidate genes, including CDR1, SOX3, SLC25A14, SLC9A6, and FGF13, have been screened in patients with X-linked dominant CMN but no causative mutations were detected (Kerrison et al 1999(Kerrison et al , 2001Zhang et al 2005). Other potential candidate genes inside the linked interval include, but are not limited to, GRIA3, MBNL3, and FHL1.…”

“…CN is commonly observed in ocular diseases such as albinism, Leber congenital amaurosis, aniridia, cone or cone-rod dystrophy, macular coloboma, optic nerve dysplasia, etc. In rare cases, CN may occur without any other known ocular or systemic disease, and is referred to as idiopathic CN or congenital motor nystagmus (CMN) (Cabot et al 1999;Kerrison et al 1999). Patients with CMN have normal or mild-to-moderately reduced visual acuity.…”

“…No gene has been identified as being responsible for CMN, although linkage studies have suggested several loci on chromosome Xp11.4-p11.3, Xq26-q27, and 6p12, for X-linked dominant (Cabot et al 1999;Kerrison et al 1999Kerrison et al , 2001Zhang et al 2005) and autosomal dominant (Kerrison et al 1996) CMN. The genetic locus for X-linked recessive CMN has not been reported.…”

Confirmation and refinement of an autosomal dominant congenital motor nystagmus locus in chromosome 1q31.3–q32.1

“…1 Nystagmus is usually associated with other ocular or systemic diseases, such as congenital cataract, albinism, Leber congenital amaurosis, aniridia, cone or cone-rod dystrophy, macular coloboma and optic nerve dysplasia that significantly impair vision early in life. 2 However, in rare cases, nystagmus occurs in the absence of other diseases, termed congenital motor nystagmus (CMN) or idiopathic congenital nystagmus, 2,3 in which case the primary defect presumably lies with ocular motor control regions of the brain rather than the normal anatomic ocular structures.…”