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Titolo:
Molecular characterization of phenylketonuria in Japanese patients
Autore:
Okano, Y; Asada, M; Kang, Y; Nishi, Y; Hase, Y; Oura, T; Isshiki, G;
Indirizzi:
Osaka City Univ, Sch Med, Dept Pediat, Abeno Ku, Osaka 5458586, Japan Osaka City Univ Osaka Japan 5458586 diat, Abeno Ku, Osaka 5458586, Japan Abeno Publ Hlth Ctr Osaka City, Osaka, Japan Abeno Publ Hlth Ctr Osaka City Osaka Japan Ctr Osaka City, Osaka, Japan Osaka Municipal Rehabil Ctr Disabled, Osaka, Japan Osaka Municipal RehabilCtr Disabled Osaka Japan Disabled, Osaka, Japan
Titolo Testata:
HUMAN GENETICS
fascicolo: 5, volume: 103, anno: 1998,
pagine: 613 - 618
SICI:
0340-6717(199811)103:5<613:MCOPIJ>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHENYLALANINE-HYDROXYLASE GENE; MISSENSE MUTATION; IN-VIVO; HYPERPHENYLALANINEMIA; PHENOTYPE; PREVALENT; GENOTYPE; POPULATION; ORIENTALS; HETEROGENEITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Okano, Y Osaka58586,Univ, Sch Med, Dept Pediat, Abeno Ku, 1-4-3 Asahimachi, Osaka 54 Osaka City Univ 1-4-3 Asahimachi Osaka Japan 5458586 i, Osaka 54
Citazione:
Y. Okano et al., "Molecular characterization of phenylketonuria in Japanese patients", HUM GENET, 103(5), 1998, pp. 613-618

Abstract

We characterized phenylalanine hydroxylase (PAH) genotypes of Japanese patients with phenylketonuria (PKU) and hyperphenylalaninemia (HPA). PKU and HPA mutations in 41 Japanese patients were identified by denaturing gradientgel electrophoresis and direct sequencing, followed by restriction fragment length polymorphism analysis to find a large deletion involving exons 5 and 6. Of 82 mutant alleles, 76 (92%) were genotyped showing 21 mutations. The major mutations were R413P (30.5%), R243Q (7.3%), R241C (7.3%), IVS4nt-1(7.3%), T278I (7.3%), E6nt-96A-->g (6.1%), Y356X (4.9%), R111X (3.7%), and442-706delE5/6 (2.4%). Eight new mutations (L52 S, delS70, S70P, Y77X, IVS3nt-1, A132 V, W187 C, and C265Y) and a polymorphism of IVS10nt-14 were detected. In vitro PAH activities of mutant PAH cDNA constructs were determined by a COS cell expression system. Six mutations, viz., R408Q, L52 S, R241 C, S70P, V388 M, and R243Q, had 55%, 27%, 25%, 20%, 16% and 10% of the in vitro PAH activity of normal constructs, respectively . The mean pretreatment phenylalanine concentration (0.83+/-0.21 mmol/l) of patients carrying theR408Q, R241 C, or L52 S mutation and a null mutation was significantly lower (P<0.0005) than that (1.99+/-0.65 mmol/l) of patients with both alleles carrying mutations associated with a severe genotype. Simple linear regression analysis showed a correlation between pretreatment phenylalanine concentrations and predicted PAH activity in 29 Japanese PKU patients (y=31.9-1.03x, r=0.59, P<0.0001). Genotype determination is useful in the prediction of biochemical and clinical phenotypes in PKU and can be of particular help in managing patients with this disorder.

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Documento generato il 05/12/20 alle ore 14:10:39