Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus

Ragge, Nicola; Hartley, Claire; Dearlove, A M; Walker, JJ; Russell‐Eggitt, Isabelle; Harris, Christopher M.

doi:10.1136/jmg.40.1.37

Cited by 34 publications

(19 citation statements)

References 25 publications

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“…28 A single gene, FRMD7 at Xq26.2 (NYS1), has been identified as causing congenital nystagmus, [29][30][31] although other loci, including NYS5, NYS2 at 6p12, NYS3 at 7p11, NYS4 at 13q31-q33 and 18q exist. 27,[32][33][34][35][36] Detailed eye assessments of individuals from families 74, V and 683 demonstrated many common features, such as early age of onset of nystagmus, horizontal nystagmus present in all directions of gaze, pendular or increasing velocity waveforms, mildly reduced VA and absence of sensory defects. The consistent finding of gaze-evoked nystagmus indicates a dysfunction of the neural integrator, which is required for all conjugate eye movements.…”

Section: Discussionmentioning

confidence: 99%

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

et al. 2009

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Section: Discussionmentioning

confidence: 99%

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

et al. 2009

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“…At least six genetic loci for CMN have been suggested, including three loci for autosomal dominant CMN (NYS2, MIM 164100, 6p12;NYS3, MIM 608345, 7p11;NYS4, MIM 193003, 13q) (Kerrison et al 1996;Klein et al 1998;Patton et al 1993;Ragge et al 2003) and three loci for X-linked CMN (NYS1, MIM 310700, Xq26-q27;NYS5, MIM 300589, Xp11.4-11.3;NYS6, MIM 300814, Xp22.3) (Cabot et al 1999;Kerrison et al 1999;Liu et al 2007). Mutation in FRMD7 has been identiWed as the most common cause of X-linked CMN (He et al 2008;Kaplan et al 2008;Schorderet et al 2007;Self et al 2007;Shiels et al 2007;Tarpey et al 2006;Zhang et al 2007a, b).…”

Section: Introductionmentioning

confidence: 99%

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Xiao

Guo

et al. 2011

Hum Genet

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Congenital motor nystagmus (CMN) is characterized by bilateral involuntary ocular oscillation without any other underlying ocular or systemic diseases. An autosomal dominant CMN was identified in a large Chinese family where all patients had nystagmus since infancy. The nystagmus in the family is independent of any known ocular or systemic diseases. After exclusion of known CMN loci, a genome-wide scan was performed by genotyping microsatellite markers at about 10 cM intervals, together with two-point linkage analysis. Exome sequencing was used to screen coding exons of well-annotated genes. Sanger-dideoxy sequencing was used to verify candidate variations inside the linkage interval. Congenital motor nystagmus in this family shows linkage to markers in a 11.39 Mb (12.1 cM) region on chromosome 1q31-q32.2 between D1S2816 and D1S2692. All nine markers in the linkage interval gave positive lod scores, with D1S2655 and D1S2636 yielding lod scores of 5.16 and 5.18, respectively, at θ = 0. No causative mutation in the linkage interval was identified by exome sequencing of gDNA from four patients. A linkage study of additional families and further analysis of candidate genes may ultimately lead to identification of the gene responsible for dominantly inherited CMN.

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“…Nystagmus has a prevalence of 1 in 1000. 1 To date, two X-linked nystagmus loci (NYS1 (Xq26.2) and NYS5 (Xp11.4)) and three autosomal loci (NYS2 (6p12), NYS3 (7p11.2) and NYS4 (13q31-q33)), [2][3][4][5][6][7] have been mapped, and the NYS1 gene has been identified as FRMD7. 2 Infantile nystagmus has also been described in association with afferent defects such as foveal hypoplasia, aniridia and iris hypoplasia.…”

Section: Introductionmentioning

confidence: 99%

Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

et al. 2013

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Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C4G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The aminoacid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.

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Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus

Cited by 34 publications

References 25 publications

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

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