Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder resulting from mutation of the proteolipid protein gene (PLP1). Clinical features of PMD include progressive psychomotor developmental delay, nystagmus, spastic quadriplegia, dystonia, and cerebellar ataxia. PMD is clinically classified into three subtypes according to the severity of the disease: connatal, transitional, and classic forms. Patients with PMD have been identified with duplication, point mutations, and deletion of PLP1. In addition, spastic paraplegia 2 (SPG2) is allelic to PMD and typically caused by missense mutations in the second extracellular domain of PLP1 or in the PLP1-specific region that is spliced out during formation of the DM20 isoform. The authors describe a Korean boy diagnosed with SPG2 caused by a mutation that results in a Pro215Leu substitution in the second extracellular domain. Analysis of phenotypes resulting from mutations affecting PLP1 has been valuable in identifying functional domains of this still incompletely understood major myelin protein. Null mutations and mutations affecting the PLP1-specific domain cause peripheral neuropathy. The PLP1-specific domain also is important in the long-term maintenance of axonal integrity. This patient's phenotype was relatively mild, in contrast with other mutations at position 215 of PLP1 that cause severe PMD. One of these severe mutations is also a missense mutation substituting an aliphatic residue, alanine, for proline. The distinct severity difference between the Pro215Leu and Pro215Ala substitutions suggests that this region of the protein is very sensitive to subtle structural changes and likely plays a critical role in PLP1 function.
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PMID:A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene. 1545 Jul 75

Congenital motor nystagmus (CMN), a subtype of nystagmus, may reduce vision or be associated with other, more serious, conditions that limit vision. The genetic basis for CMN is still unknown. To identify a locus for CMN, genotyping and linkage analysis were performed in 22 individuals from a Chinese family with X-linked CMN using markers from X chromosome. The maximum LOD score obtained for microsatellite maker DXS1192 linked the CMN locus in this family to Xq. By haplotype construction the locus for CMN was finally localized to an approximately 4.4-cM region at chromosome Xq26.3-q27.1. The SLC9A6 and FGF13 genes in this region, were selected and screened for mutation in this family, but no mutation was detected.
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PMID:Confirmation and refinement of a genetic locus of congenital motor nystagmus in Xq26.3-q27.1 in a Chinese family. 1551 95

To investigate the relationship between X chromosome and obligatory gene of a pedigree with congenital nystagmus,we used the following markers: DXS1214, DXS1068, DXS993, DXS8035, DXS1047, DXS8033, DXS1192 and DXS1232. Genome screening and genotyping were conducted in this pedigree of congenital nystagmus, and linkage analysis by LINKAGE package was used to determine the potential location. The linkage was not found on the Xp (All LOD score <-1) but on Xq (the maximum LOD score=2). The related gene of this pedigree was located on the long arm of X chromosome. We demonstrate that Xq26-Xq28 is a common locus for CMN. It bring us closer to the identification of a gene responsible for X-linked CMN.
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PMID:[Mapping of a pedigree with congenital nystagmus]. 1564 35

Cerebellar vermis aplasia (ACV, OMIM 117360) is a rare malformation of the cerebellum, with only few familial patients reported so far. Main clinical features of this rare disorder include floppiness and delayed milestones in early infancy, preceding mild cerebellar ataxia, non-progressive clinical course, normal or slightly delayed intelligence, and occasional nystagmus. Neuroimaging reveals selective involvement of the cerebellum, which is prominent in the vermis. Because of the large preponderance of female patients, X-linked dominant transmission was suggested by [Fenichel and Phillips (1989); Arch Neurol 46:582-583], and subsequent reports only concern female patients. Only one family with male-to-male transmission presenting with a generalized atrophy of the cerebellum rather than a more localized vermis aplasia has been reported so far. We report on a family in which father and son are affected by a mild form of ACV, thus confirming an autosomal mode of inheritance of the disease. Our patients showed a progressive improvement of their motor abilities, neurological examination of the father being actually normal except for a mild mental retardation. We also evaluated the potential role of two candidate genes, EN2 and ZIC1, responsible for abnormal cerebellar development in murine knock-out models. However, molecular analysis failed to reveal any causative mutation in the coding sequence of the two genes in our patients. The understanding of the genetic basis of autosomal dominant ACV would allow a better classification of isolate cerebellar malformations and might permit to understand cell differentiation and migration in the developing central nervous system.
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PMID:Cerebellar vermis aplasia: patient report and exclusion of the candidate genes EN2 and ZIC1. 1594 Jun 96

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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PMID:The molecular genetics of congenital idiopathic nystagmus. 1670 75

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.
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PMID:Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. 1701 95

Congenital nystagmus is an eye movement disorder in which one or both eyes are in constant movement. It can be associated with a number of ocular or neurological diseases, or it can be inherited in an autosomal or X-linked fashion. The latter form is called idiopathic or motor nystagmus (CIN). Loci on the X chromosome (NYS1) and on 6p12 (NYS2), 7p11.2 (NYS3), and 13q31-q33 (NYS4) have been identified for CIN. The molecular characterization of NYS1 has recently been solved by Tarpey et al., who identified mutations in FRMD7, a gene of unclear function. We report five novel mutations in FRMD7 and confirm the role of this gene in the pathogenesis of X-linked congenital nystagmus.
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PMID:Novel mutations in FRMD7 in X-linked congenital nystagmus. Mutation in brief #963. Online. 1739 53

Incontinentia pigmenti is a rare, X-linked dominant, genodermatosis and is almost always lethal in males. It is characterized by cutaneous, ocular, dental, and central nervous system (CNS) abnormalities and about 35% of patients develop some form of ocular abnormality, which may include retinal vascular abnormalities, ischemic retinal infarctions, retinal detachments, cataracts, uveitis, strabismus, and nystagmus. Incontinentia pigmenti has been linked to the NEMO gene, which is mapped to Xq28.
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PMID:Fluorescein angiographic findings in a male infant with incontinentia pigmenti. 1749 89

Congenital stationary night blindess-2 (incomplete congenital stationary night blindness (iCSNB) or CSNB-2) is a nonprogressive, X-linked retinal disease which can lead to clinical symptoms such as myopia, hyperopia, nystagmus, strabismus, decreased visual acuity, and impaired scotopic vision. These clinical manifestations are linked to mutations found in the CACNA1F gene which encodes for the Ca(v)1.4 voltage-gated calcium channel. To better understand the physiological effects of these mutations, three missense mutants, F742C, G1007R and R1049W, previously shown to be mutated in patients with CSNB-2, were transiently expressed in human embryonic kidney (HEK) tsA-201 cells and characterized using whole-cell patch clamp. The G1007R mutation is located in transmembrane segment 5 (S5) of domain III and R1049W is located in the extracellular linker between S5 and the P-loop of domain III. Both mutants produced full length proteins that targeted to the membrane but did not support ionic currents. In 20 mM Ba(2+), F742C (S6 domain II) produced a approximately 21 mV hyperpolarizing shift in half activation potential (V(a[1/2])) and a approximately 23 mV hyperpolarizing shift in half inactivation potential (V(h[1/2])). Additionally, F742C displayed slower inactivation kinetics and a smaller whole cell conductance (G(max)). In physiological 2 mM Ca(2+), F742C produced a approximately 19 mV hyperpolarizing shift in V(a[1/2]). These findings suggest that the pathology of CSNB-2 in patients with these missense mutations in the Ca(v)1.4 calcium channel is the result in either a gain of function (F742C) or a loss of function (G1007R, R1049W).
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PMID:Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W. 1794 18

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 only one disease gene has been identified (FRMD7, Xq26.2). The pathophysiological mechanisms underlying nystagmus are poorly understood but it is anticipated that characterization of the FRMD7 gene and identification of novel nystagmus genes will provide insights into this condition and the functioning and development of the visual pathways in general.
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PMID:A review of the molecular genetics of congenital Idiopathic Nystagmus (CIN). 1816 16


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