Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency

Sakamoto, Osamu; Suzuki, Yôichi; Aoki, Yoko; Li, X.; Hiratsuka, Masahiro; Yanagihara, Kana; Inui, Kentaro; Okabe, Takahiro; Yamaguchi, S.; Kudoh, Jun; Shimizu, Nobuyoshi; Narisawa, Kuniaki

doi:10.1023/a:1005435121933

Cited by 11 publications

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“…The 997T Ͼ C (237Leu Ͼ Pro) and the 1067delG mutations were screened, using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP), as described (Aoki et al 1995). The 508Arg Ͼ Trp (1809C Ͼ a Underlined haplotypes represent mutant alleles T), 565Arg Ͼ Ter (1980C Ͼ T) and 550Val Ͼ Met (1935G Ͼ A) mutations were determined by direct sequencing, as described (Aoki et al 1997;Sakamoto et al 1998). …”

Section: Mutation In Hcs-deficient Patientsmentioning

confidence: 99%

“…The mutations 237Leu Ͼ Pro (nucleotide change 997T Ͼ C) and 1067delG predominated only among the Japanese patients. The 508Arg Ͼ Trp (1809C Ͼ T) mutation has been found in two unrelated Japanese patients (Sakamoto et al 1998), as well as in non-Japanese patients (Dupuis et al 1996). The 550Val Ͼ Met (1935G Ͼ A) mutation has also been found in many ethnic groups (Dupuis et al 1996;Aoki et al 1997;Zammarchi et al 1998).…”

Section: Introductionmentioning

confidence: 97%

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Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations

et al. 2000

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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 Ͼ Pro (seven alleles) and 1067delG (five alleles) were predominant; 508Arg Ͼ Trp and 550Val Ͼ 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 Ͼ 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 Ͼ Trp alleles were associated with several haplotypes, including 2-3 and 1-4. The haplotype of a Taiwanese patient homozygous for the 508Arg Ͼ Trp mutation was 2-3/2-3. The haplotype of one Japanese patient homozygous for the 550Val Ͼ 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 Ͼ Trp and 550Val Ͼ Met occurred at CpG dinucleotide. The data suggest that these two mutations represent a mutational hot-spot.

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Section: Mutation In Hcs-deficient Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations

et al. 2000

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Holocarboxylase Synthetase

Narisawa¹

2002

Wiley Encyclopedia of Molecular Medicine

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Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency

et al. 2002

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Holocarboxylase synthetase (HLCS) deficiency (HLCSD) is a rare autosomal recessive disorder of biotin metabolism. HLCS catalyzes the biotinylation of the four human biotin-dependent carboxylases. Using the newly available human genomic sequence, we report the map of HLCS genomic structure and the predicted exon/intron boundaries. Moreover, the molecular studies of four patients (two Italians, one Iranian, and one Australian) affected by HLCS deficiency are here reported. The clinical findings, the age of onset, and response to biotin treatment differed between our patients. The diagnosis was made by organic acid analysis and confirmed by enzymatic analysis in three patients. Six mutations in the HLCS gene were identified, including two novel (N511K and G582R) and four known missense mutations (L216R, R508W, V550M, and G581S). Five of the mutations are localized within the HLCS biotin-binding domain, whereas the L216R amino acid change is located in the N-terminal region outside of the putative biotin-binding domain. This mutation, previously reported in a heterozygous state, was detected for the first time in a patient with homozygous status. The patient's severe clinical phenotype and partial responsiveness to biotin support a genotype-phenotype correlation through the involvement of residues of the N-terminal region in a substrate specificity recognition or regulation of the HLCS enzyme.

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Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency

Cited by 11 publications

References 3 publications

Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations

Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations

Holocarboxylase Synthetase

Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency

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