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  • 1
    ISSN: 1432-1076
    Keywords: Key words Biotin ; Holocarboxylase synthetase ; Multiple carboxylase deficiency ; Splice error
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabolism characterised by metabolic ketoacidosis and skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this disease is usually between the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the patient developed his first episode of acidosis at age 8 years and had an exceptionally slow response to biotin therapy. A homozygous mutation was identified at the +5 position of the splice donor site in intron 10 of the HCS gene (IVs10 + 5(g → a)), resulting in abnormal splicing of HCS mRNA. A moderate decrease in the amount of normal HCS mRNA may account for the atypical, late-onset phenotype of this patient. Conclusion Molecular analysis is a useful tool for understanding the phenotypic variations in holocarboxylase synthetase deficiency.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant breeding 119 (2000), S. 0 
    ISSN: 1439-0523
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Effects of the resistant cultivars of melon on the powdery mildew fungus, Sphaerotheca fuliginea, were investigated in a melon-growing area of Japan. Powdery mildew fungi were isolated from four melon cultivars (‘HN21’, ‘Quincy’, ‘Earl's Knight Natsu 2’ and ‘Earl's Miyabi Natsu 2′) which are resistant to different races of S. fuliginea.‘HN21’is resistant to races 1 and N1,‘Quincy’ and ‘Earl's Knight Natsu 2’are resistant to races 1 and N2, and ‘Earl's Miyabi Natsu 2’is resistant to races 1, N1 and N2. All 155 strains isolated from ‘HN21’were identified as race N2. Seventy out of 81 strains isolated from ‘Quincy’ and ‘Earl's Knight Natsu 2’were identified as race N1, while other strains were identified as races 1, 2US, N2 and N3. Nineteen out of 29 strains isolated from ‘Earl's Miyabi Natsu 2’were identified as race N3, while other strains were identified as races 10, 2US, N1 and N4. These results suggest that, although the resistant cultivars are extremely effective for protecting the plants from their respective races, a race succession rapidly takes place, even in a small area, and other minor races become predominant.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (ψ GLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The ψ GLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that ψ GLDC is a processed pseudogene that arose from the GLDC transcript about 4–8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1–3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using ψ GLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and ψ GLDC should facilitate the molecular analysis of NKH.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-232X
    Keywords: Key words Holocarboxylase synthetase ; Multiple carboxylase deficiency ; Biotin ; Mutation ; Microsatellite markers ; Haplotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Holocarboxylase synthetase (HCS) deficiency is a rare autosomal recessive disorder of biotin metabolism. Including three new Japanese patients we diagnosed in this study, ten Japanese families have, so far, been accumulated. In these families, the mutations 237Leu 〉 Pro (sevenalleles) and 1067delG (five alleles) were predominant; 508Arg 〉 Trp and 550Val 〉 Met mutations were identified in three families in the heterozygous form and in one patient in the homozygous form, respectively. To determine the origin of these mutations, we identified new polymorphic microsatellite markers in the HCS gene and analyzed the haplotypes of the patients. All the 237Leu 〉 Pro and the 1067delG alleles were associated with haplotype 2-2. This finding is consistent with the notion that these mutations are founder mutations in the Japanese population. Three Japanese 508Arg 〉 Trp alleles were associated with several haplotypes, including 2-3 and 1-4. The haplotype of a Taiwanese patient homozygous for the 508Arg 〉 Trp mutation was 2-3/2-3. The haplotype of one Japanese patient homozygous for the 550Val 〉 Met mutation was 1-4/1-4, whereas that of a Jewish patient with the same homozygous mutation was 2-3/2-3. Both mutations were associated with at least two haplotypes and were found in several ethnic groups. The changes 508Arg 〉 Trp and 550Val 〉 Met occurred at CpG dinucleotide. The data suggest that these two mutations represent a mutational hot-spot.
    Type of Medium: Electronic Resource
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