Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety-four consecutive patients admitted for elective cataract surgery were prospectively examined for erythrocyte galactokinase activity. The presumed etiology for the cataract was established by history and physical examination in 51 patients (21 were diabetic). The cataract was classified as idiopathic in 43 patients. Galactokinase activity was significantly lower in idiopathic vs. presumed (nondiabetic) etiology patients 50 years of age or younger (P less than 0.05) and in idiopathic cataract patients 50 years of age or younger vs. those older than 51 years of age (P = 0.0033). Three of the idiopathic cataract patients (6.9%) had galactokinase levels less than two standard deviations below the mean galactokinase level for age-matched patients with suspected (nondiabetic) etiology. Compared with the expected distribution for the heterozygote in the general population (0.2%), this was highly significant (P = 0.0001). Diminished galactokinase activity may increase the risk of developing presenile cataracts requiring surgery by the fourth decade.
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PMID:Galactokinase activity in patients with idiopathic cataracts. 395 27

Galactokinase (GALK) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet. We characterized the human GALK gene by screening a Japanese genomic DNA phage library, and found that several nucleotides in the 5'-untranslated region and introns 1,2, and 5 in our GALK genomic analysis differed from published data. A 20-bp tandem repeat was found in three places in intron 5, which were considered insertion sequences. We identified five novel mutations in seven unrelated Japanese patients with GALK deficiency. There were three missense mutations and two deletions. All three missense mutations (R256W, T344M, and G349S) occurred at CpG dinucleotides, and the T344M and G349S mutations occurred in the conserved region. The three missense mutations led to a drastic reduction in GALK activity when individual mutant cDNAs were expressed in a mammalian cell system. These findings indicated that these missense mutations caused GALK deficiency. The two deletions, of 410delG and 509-510delGT, occurred at the nucleotide repeats GGGGGG and GTGTGT, respectively, and resulted in in-frame nonsense codons at amino acids 163 and 201. These mutations arose by slipped strand mispairing. All five mutations occurred at hot spots in the CpG dinucleotide for missense mutations and in short direct repeats for deletions. These five mutations in Japanese have not yet been identified in Caucasians. We speculate that the origin of GALK mutations in Japanese is different from that in Caucasians.
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PMID:Molecular characterization of galactokinase deficiency in Japanese patients. 1057 Sep 8

Galactokinase (GK; EC 2.7.1.6) is the first enzyme in the metabolism of galactose. In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens. In an attempt to make a galactosemic animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene targeting. As expected, galactose was very poorly metabolized in GK-deficient mice. In addition, both galactose and galactitol accumulated in tissues of GK-deficient mice. Surprisingly, the GK-deficient animals did not form cataracts even when fed a high galactose diet. However, the introduction of a human aldose reductase transgene into a GK-deficient background resulted in cataract formation within the first postnatal day. This mouse represents the first mouse model for congenital galactosemic cataract.
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PMID:A mouse model of galactose-induced cataracts. 1091 71

Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by hypergalactosemia and cataract formation. Through mass screening of newborn infants, we identified a novel and prevalent GALK variant (designated here as the "Osaka" variant) associated with an A198V mutation in three infants with mild GALK deficiency. GALK activity and the amount of immunoreactive protein in the mutant were both 20% of normal construct in expression analysis. The K(m) values for galactose and ATP-Mg(2+) in erythrocytes with homozygous A198V were similar to those of the healthy adult control subjects. A population study for A198V revealed prevalences of 4.1% in Japanese and 2.8% in Koreans, lower incidence in Taiwanese and Chinese, no incidence in blacks and whites from the United States, and a significantly high frequency (7.8%; P < .023) in Japanese individuals with bilateral cataract. This variant probably originated in Japanese and Korean ancestors and is one of the genetic factors that causes cataract in elderly individuals.
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PMID:A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, "Osaka," in Asians. 1123 2

Galactokinase (GALK1) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet. Galactokinase deficiency results from mutation in the GALK1 gene mapped on 17q24. Since GK1 cDNA was cloned about 20 mutations (prevalently deletions and missense) have been reported to date. Most of these reported mutations are confined to single families, and only one of them, P28T, has been referred as the founder Romani mutation. In this paper we report two novel missense mutations in GALK1 gene, identified in two unrelated patients with galactokinase deficiency. One mutation, g.575G>A, substitutes a valine for a methionine at amino acid 32 (p.V32M), while the other mutation, g.2839G>A, results in the arginine to glutamine substitution p.R239Q (GenBank sequence L76927). Biochemical studies demonstrate that these mutations led to a drastic modification in GALK activity when individual mutant cDNAs were expressed in an E. coli system. These findings indicate the pathogeneticity of these mutations causing GALK deficiency.
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PMID:Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency. 1502 38