Hereditary congenital nystagmus and gaze‐holding failure

Dell’Osso, Louis F.; Weissman, BM; Leigh, R. John; Abel, Larry A; Sheth, N.V.

doi:10.1212/wnl.43.9.1741

Cited by 27 publications

(10 citation statements)

References 21 publications

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“…Reasons for incomplete penetrance among female carriers include patterns of skewed X inactivation, interactions with other genes, and nongenetic, developmental influences on oculomotor development. In some instances, unaffected relatives, who do not manifest nystagmus, may nevertheless have subclinical eye movement abnormalities demonstrated by sensitive recording techniques (Dell'Osso et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Congenital Motor Nystagmus Linked to Xq26-q27

Kerrison¹,

Vagefi²,

Barmada

et al. 1999

The American Journal of Human Genetics

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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.

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Section: Discussionmentioning

confidence: 99%

Congenital Motor Nystagmus Linked to Xq26-q27

Kerrison¹,

Vagefi²,

Barmada

et al. 1999

The American Journal of Human Genetics

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“…Subtle eye movement abnormalities have been detected among apparently unaffected relatives of CIN patients (Dell'Osso & Weissman, 1993;Shallo-Hoffmann & Watermeier, 1988) and it is also known that nystagmus waveform and phenotype may vary significantly, not only within pedigrees but even monozygotic twins with CIN. (Abadi & Dickinson, 1983;Spooner & Bateman, 1986) This may be of considerable importance for linkage projects using these CIN pedigrees where phenotypic variations may lead to errors in assigning affected/non-affected status.…”

Section: X-linked Cinmentioning

confidence: 99%

“…There are good reasons for this: (1) there is a high frequency of afferent visual-pathway dysfunctions; (2) CN damping by use of contact lenses and cutaneous stimulation of the trigeminal nerve; (3) the presence of a null zone; (4) neurological origin of acquired nystagmus in adults; and (5) requirement of a functioning geniculostriate system for the development of horizontal CN. Several proposed mechanisms behind CIN have been suggested but are currently out of favor; these include the presence of a leaky neural integrator (Dell'Osso et al, 1993), misdirection of the retinogeniculate or subcortical visual pathway (Fielder and Evans 1988), and albinolike abnormal chiasmatic decussation of the optic axons (Apkarian & Shallo-Hoffman, 1991).…”

Section: Candidate Genesmentioning

confidence: 99%

The Molecular Genetics of Congenital Idiopathic Nystagmus

Self

Lotery

2006

Seminars in Ophthalmology

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Congenital Idiopathic Nystagmus (CIN) is genetically heterogeneous. Autosomal dominant, autosomal recessive and X-linked patterns of inheritance have been reported. Linkage analysis has suggested the existence of at least three distinct loci for both autosomal dominant and x-linked forms, although as yet no disease genes have been identified. The pathophysiological mechanisms underlying nystagmus are poorly understood and it is likely that insights may arise from finding and characterizing disease genes. If linkage experiments are used to find "nystagmus genes," their power will depend heavily on accurate phenotyping to avoid misdiagnosis due to masquerading conditions and phenotypic variations within pedigrees.

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“…However, in IIN, other than reduced visual acuity and an abnormal optokinetic response (9,10), no overt ocular abnormality has been described. This has led to a number of mathematical models suggesting that infantile nystagmus arises due to the instability of the neural integrator (11,12) or the smooth pursuit system (13), rather than an afferent defect.…”

Section: Introductionmentioning

confidence: 99%

Abnormal retinal development associated with FRMD7 mutations

Thomas

Crosier

Lindsay

et al. 2014

Human Molecular Genetics

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Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.

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Hereditary congenital nystagmus and gaze‐holding failure

Cited by 27 publications

References 21 publications

Congenital Motor Nystagmus Linked to Xq26-q27

Congenital Motor Nystagmus Linked to Xq26-q27

The Molecular Genetics of Congenital Idiopathic Nystagmus

Abnormal retinal development associated with FRMD7 mutations

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