Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities, including corneal opacities, retinal degeneration, and strabismus. Severely affected as well as milder patients have been described. Over 80% of the MLIV patients are Ashkenazi Jews; the estimated heterozygote frequency in this population is 1/100. The disease is classified as a mucolipidosis due to the simultaneous lysosomal storage of lipids together with water-soluble substances. A broad spectrum of lipids and acid mucopolysaccharides were identified as the storage substances. Kinetic studies demonstrated that this heterogeneous storage stems from an abnormal endocytosis process in cells from MLIV patients of membrane components from late endosomes to the lysosomes and/or delayed efflux to the Golgi apparatus. The MLIV gene was mapped to chromosome 19p13.2--13.3 where a novel gene, MCOLN1, with MLIV-causing mutations, was identified. Two mutations were found among 95% of the Ashkenazi MLIV alleles, including an intronic acceptor splice-site mutation in 72% of the alleles and a partial gene deletion in 23%. Each of these mutations was associated with a defined haplotype in this chromosomal region. Other mutations were mostly identified in single, Ashkenazi and non-Ashkanazi patients, including missense, nonsense nucleotide deletions, and insertions. All mutations but one were identified in patients exhibiting the severe phenotype, an in-frame amino acid deletion was identified in a mild patient. MCOLN1 encodes a 580 aa protein, mucolipin 1, which is a member of a new protein family of unknown function at present, the mucolipins. Mucolipin 1 is a membrane protein with 6 transmembrane domains, a serine lipase, and nuclear localization signal motives. The protein shows homology to a group of calcium channels of the TRP/TRPL family. The involvement of this protein in the endocytosis process of membrane components is currently studied. A population screening operation among the Ashkenazi population for the detection of heterozygotes has been started in Israel as a prevention program.
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PMID:Mucolipidosis type IV. 1146 Nov 86

A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.
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PMID:Candidate loci for Zimmermann-Laband syndrome at 3p14.3. 1716 23

We have investigated a consanguineous Iranian family with eight patients who suffer from mental retardation, disturbed equilibrium, walking disability, strabismus and short stature. By autozygosity mapping we identified one region with a significant LOD score on chromosome 9(p24.2-24.3). The interval contains the VLDLR gene, which codes for the very low-density lipoprotein receptor. This protein is part of the reelin signalling pathway, which is involved in neuroblast migration in the cerebral cortex and cerebellum. A homozygous deletion encompassing VLDLR has previously been found to cause a syndrome of cerebellar ataxia and mental retardation associated with cerebellar hypoplasia in the Hutterite population known as dysequilibrium syndrome (DES). The reported deletion however, contains an additional brain expressed gene of unknown function, whose involvement in the aetiology of the phenotype could so far not be excluded. We screened the coding region of VLDLR for mutations in our patients and found a homozygous c.1342C>T nucleotide substitution, which leads to a premature stop codon in exon 10. This is the first report of a mutation in patients with DES that affects VLDLR exclusively, confirming the central role of the very low-density lipoprotein receptor in the aetiology of this condition.
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PMID:Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome. 1804 14

In Arabidopsis thaliana, flowers are determinate, showing a fixed number of whorls. Here, we report on three independent genes, a novel gene REBELOTE (RBL; protein of unknown function), SQUINT (SQN; a cyclophilin), and ULTRAPETALA1 (ULT1; a putative transcription factor) that redundantly influence floral meristem (FM) termination. Their mutations, combined with each other or with crabs claw, the genetic background in which they were isolated, trigger a strong FM indeterminacy with reiterations of extra floral whorls in the center of the flower. The range of phenotypes suggests that, in Arabidopsis, FM termination is initiated from stages 3 to 4 onwards and needs to be maintained through stage 6 and beyond, and that RBL, SQN, and ULT1 are required for this continuous regulation. We show that mutant phenotypes result from a decrease of AGAMOUS (AG) expression in an inner 4th whorl subdomain. However, the defect of AG activity alone does not explain all reported phenotypes, and our genetic data suggest that RBL, SQN, and, to a lesser extent, ULT1 also influence SUPERMAN activity. Finally, from all the molecular and genetic data presented, we argue that these genes contribute to the more stable and uniform development of flowers, termed floral developmental homeostasis.
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PMID:REBELOTE, SQUINT, and ULTRAPETALA1 function redundantly in the temporal regulation of floral meristem termination in Arabidopsis thaliana. 1844 Dec 15