Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the ophthalmological findings of a 6-year-old boy who has features of both Aland Island eye disease (also called Forsius-Eriksson ocular albinism) and incomplete congenital stationary night blindness, as defined by Miyake, leading us to suspect that they are the same entity. This child has a deletion of part of band 21 of the short arm of the X chromosome (Xp21) and three other X-linked disorders: congenital adrenal hypoplasia, glycerol kinase deficiency, and Duchenne type muscular dystrophy. The electroretinogram showed negative scotopic and abnormal photopic waveforms that were similar, if not identical, to the electroretinographic findings in both Aland Island eye disease and X-linked incomplete congenital stationary night blindness. Because of this similarity and the defective dark adaptometry that has been reported in patients with this disorder, we believe that Aland Island eye disease is more appropriately classified as a form of congenital night blindness than as a form of ocular albinism. From our case and review of the literature, Aland Island eye disease and incomplete congenital stationary night blindness appear indistinguishable. If further studies confirm that the disorders are the same, we recommend use of the term Aland Island eye disease or Forsius-Eriksson-Miyake syndrome. We also recommend that the gene symbols CSNB1 and CSNB2 be used for complete congenital stationary night blindness and Aland disease, respectively.
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PMID:Aland Island eye disease (Forsius-Eriksson syndrome) associated with contiguous deletion syndrome at Xp21. Similarity to incomplete congenital stationary night blindness. 266 10

The human Xp11.23-p11.22 interval has been implicated in several inherited diseases including Wiskott-Aldrich syndrome; three forms of X-linked hypercalciuric nephrolithiaisis; and the eye disorders retinitis pigmentosa 2, congenital stationary night blindness, and Aland Island eye disease. In constructing YAC contigs spanning Xp11. 23-p11.22, we have previously shown that the region around the synaptophysin (SYP) gene is refractory to cloning in YACs, but highly stable in cosmids. Preliminary analysis of the latter suggested that this might reflect a high density of coding sequences and we therefore undertook the complete sequencing of a SYP-containing cosmid. Sequence data were extensively analyzed using computer programs such as CENSOR (to mask repeats), BLAST (for homology searches), and GRAIL and GENE-ID (to predict exons). This revealed the presence of 29 putative exons, organized into three genes, in addition to the 7 exons of the complete SYP coding region, all mapping within a 44-kb interval. Two genes are novel, one (CACNA1F) showing high homology to alpha1 subunits of calcium channels, the other (LMO6) encoding a product with significant similarity to LIM-domain proteins. RT-PCR and Northern blot studies confirmed that these loci are indeed transcribed. The third locus is the previously described, but not previously localized, A4 differentiation-dependent gene. Given that the intron-exon boundaries predicted by the analysis are consistent with previous information where available, we have been able to suggest the genomic organization of the novel genes with some confidence. The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6. The order of loci was Xpter-A4-LMO6-SYP-CACNA1F-Xcen, with intergenic distances ranging from approximately 300 bp to approximately 5 kb. The density of transcribed sequences in this area (>80%) is comparable to that found in the highly gene-rich chromosomal band Xq28. Further studies may aid our understanding of the long-range organization surrounding such gene-enriched regions.
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PMID:Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp. 934 58

X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by disturbed or absent night vision; its clinical features may also include myopia, nystagmus, and impaired visual acuity. X-linked CSNB is clinically heterogeneous, and it may also be genetically heterogeneous. We have studied 32 families with X-linked CSNB, including 11 families with the complete form of CSNB and 21 families with the incomplete form of CSNB, to identify genetic-recombination events that would refine the location of the disease genes. Critical recombination events in the set of families with complete CSNB have localized a disease gene to the region between DXS556 and DXS8083, in Xp11.4-p11.3. Critical recombination events in the set of families with incomplete CSNB have localized a disease gene to the region between DXS722 and DXS8023, in Xp11.23. Further analysis of the incomplete-CSNB families, by means of disease-associated-haplotype construction, identified 17 families, of apparent Mennonite ancestry, that share portions of an ancestral chromosome. Results of this analysis refined the location of the gene for incomplete CSNB to the region between DXS722 and DXS255, a distance of 1.2 Mb. Genetic and clinical analyses of this set of 32 families with X-linked CSNB, together with the family studies reported in the literature, strongly suggest that two loci, one for complete (CSNB1) and one for incomplete (CSNB2) X-linked CSNB, can account for all reported mapping information.
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PMID:Evidence for genetic heterogeneity in X-linked congenital stationary night blindness. 952 39

The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific calcium channel alpha1-subunit gene (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and showing high homology to L-type calcium channel alpha1-subunits. Mutation analysis in 13 families with CSNB2 revealed nine different mutations in 10 families, including three nonsense and one frameshift mutation. These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2.
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PMID:An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. 966 99

X-linked congenital stationary night blindness (CSNB) is a recessive non-progressive retinal disorder characterized by night blindness, decreased visual acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X-linked CSNB have been proposed. Patients with complete CSNB show moderate to severe myopia, undetectable rod function and a normal cone response, whereas patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but measurable rod and cone function. The electrophysiological and psychophysical features of these clinical entities suggest a defect in retinal neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects the recently described genetic heterogeneity in which the locus for complete CSNB (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the CSNB2 minimal region was characterized and found to have similarity to voltage-gated L-type calcium channel alpha1-subunit genes. Mutation analysis of this new alpha1-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six different mutations that are all predicted to cause premature protein truncation. These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.
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PMID:Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. 966

Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by night blindness, nystagmus, myopia, a variable decrease in visual acuity, an abnormal electroretinographic response, and a disturbance in dark adaptation. Two forms of X-linked CSNB have been defined, complete CSNB in which rod function is extinguished, and incomplete CSNB in which rod function is reduced but not extinguished, as seen by electroretinography and dark adaptometry. In studying a large family of Mennonite ancestry, we have confirmed linkage between the locus (CSNB2) for incomplete CSNB and genetic markers in the Xp11 region. In particular, lod scores of 12.25 and 15.26 at zero recombination were observed between CSNB2 and the markers DXS573 and DXS255. Detailed analysis of critical recombinant chromosomes in this extended family have refined the minimal region for the CSNB2 locus to the interval between DXS6849 and DXS8023 in Xp11.23.
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PMID:Localization of a gene for incomplete X-linked congenital stationary night blindness to the interval between DXS6849 and DXS8023 in Xp11.23. 976 Jan 93

X-linked congenital stationary night blindness (CSNBX) is a hereditary non-progressive retinal disorder, which can appear in two different clinical forms, complete and incomplete, associated with CSNB1 and CSNB2 loci on Xp. We describe a Sardinian family with complete CSNBX and define better the limits of the CSNB1 genetic locus on Xp11.4 through linkage analysis. Haplotype analysis showed two key recombinants, which restrict the CSNB1 locus to a region of about 3 cM limited by markers DSX1068 and DSX6810 respectively. The locus that we describe is included in the CSNB1 locus defined by previous reports referring to the same clinical form of the disease. These results, in addition to other recent mapping reports about families from different geographical areas, confirm the genetic homogeneity of X-linked complete CSNB.
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PMID:Complete congenital stationary night blindness maps on Xp11.4 in a Sardinian family. 1043 64

The mutant L-type calcium channel alpha(1)-subunit gene, CACNA1F, was recently identified as the gene responsible for incomplete X-linked congenital stationary night blindness. The 6070-bp mRNA transcript is predicted to encode a 1977-amino-acid pore-forming protein with cytoplasmic amino- and carboxyl-termini separated by four homologous repeat domains, each consisting of six transmembrane segments. CACNA1F has been shown to be preferentially expressed in the retina, indicative of a specific functional role in visual processing. We have established the complete sequence of the murine orthologue of CACNA1F, namely Cacna1f. The total length of the mRNA transcript of the murine gene was established to be 6080 bp with an open reading frame that translates into a 1985-amino-acid protein. Cacna1f is highly homologous to the human sequence, with 90% identity at the amino acid level and almost perfect conservation between the functional domains. Furthermore, as in the human gene, the 3' end of the Cacna1f gene maps within 5 kb of the 5' end of the mouse synaptophysin gene in a region orthologous to Xp11.23. Using in situ hybridization, Cacna1f was found to be expressed in the inner and outer nuclear layers and the ganglion cell layer of the retina.
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PMID:Isolation and characterization of a calcium channel gene, Cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness. 1087 87

X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by impaired night vision, variably involving high myopia, nystagmus, decreased visual acuity, and strabismus. Linkage studies have identified two distinct loci for X-linked CSNB1 and CSNB2 on the short arm of chromosome X. The gene mutated in families displaying the "incomplete phenotype" of CSNB (i.e., CSNB2) has recently been identified. To identify novel candidate genes for the "complete form" of CSNB (i.e., CSNB1) we screened the physically vast region Xp11.3-Xp11.4 for cDNA sequences. This led us to identify and map the G protein coupled receptor (GPCR) gene GPR34 to Xp11.4 within 650 kb of the marker DXS993. Deletion screening via Southern blotting and direct sequencing of GPR34 revealed no mutations in 19 unrelated men with CSNB1, excluding a causal role in the disease. However, because of its expression in retinal and neural tissue and the involvement of GPCRs in transmembrane signal transduction, GPR34 remains a putative candidate gene for a number of ocular diseases which also map to the Xp11.4 region.
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PMID:Physical mapping and exclusion of GPR34 as the causative gene for congenital stationary night blindness type 1. 1098 42

X-linked congenital stationary night blindness (XLCSNB) is characterized by impaired scotopic vision with associated ocular symptoms such as myopia, hyperopia, nystagmus and reduced visual acuity. Genetic mapping in families with XLCSNB revealed two different loci on the proximal short arm of the X chromosome. These two genetic subtypes can be distinguished on the basis of electroretinogram (ERG) responses and psychophysical testing as a complete (CSNB1) and an incomplete (CSNB2) form. The CSNB1 locus has been mapped to a 5-cM linkage interval in Xp11.4 (refs 2,5-7). Here we construct and analyse a contig between the markers DXS993 and DXS228, leading to the identification of a new gene mutated in CSNB1 patients. It is partially deleted in 3 families and mutation analysis in a further 21 families detected another 13 different mutations. This gene, designated NYX, encodes a protein of 481 amino acids (nyctalopin) and is expressed at low levels in tissues including retina, brain, testis and muscle. The predicted polypeptide is a glycosylphosphatidylinositol (GPI)-anchored extracellular protein with 11 typical and 2 cysteine-rich, leucine-rich repeats (LRRs). This motif is important for protein-protein interactions and members of the LRR superfamily are involved in cell adhesion and axon guidance. Future functional analysis of nyctalopin might therefore give insight into the fine-regulation of cell-cell contacts in the retina.
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PMID:The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. 1106 72


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