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Titolo:
Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acidexchange
Autore:
Dvorakova, L; Storkanova, G; Unterrainer, G; Hujova, J; Kmoch, S; Zeman, J; Hrebicek, M; Berger, J;
Indirizzi:
First Fac Med, Inst Inherited Metab Disorders, Prague 12808, Czech Republic First Fac Med Prague Czech Republic 12808 , Prague 12808, Czech Republic Gen Fac Hosp, Prague 12808, Czech Republic Gen Fac Hosp Prague Czech Republic 12808 p, Prague 12808, Czech Republic Ctr Integrated Genom, Prague, Czech Republic Ctr Integrated Genom PragueCzech Republic enom, Prague, Czech Republic Univ Vienna, Brain Res Inst, Vienna, Austria Univ Vienna Vienna AustriaUniv Vienna, Brain Res Inst, Vienna, Austria
Titolo Testata:
HUMAN MUTATION
fascicolo: 1, volume: 18, anno: 2001,
pagine: 52 - 60
SICI:
1059-7794(2001)18:1<52:ENAGMA>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATP-BINDING DOMAIN; MISSENSE MUTATIONS; GONADAL MOSAICISM; ALD GENE; IDENTIFICATION; DEFICIENCY; PROTEIN; THERAPY; PHENOTYPES; DIAGNOSIS;
Keywords:
adrenoleukodystrophy; X-linked; X-ALD; adrenomyeloneuropathy; Addison disease; ALDP; ABCD1; peroxisome; neurodegeneration; very long-chain fatty acid; VLCFA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Hrebicek, M First Fac Med, Inst Inherited Metab Disorders, Ke Karlovu 2, Prague 12808,Czech Republic First Fac Med Ke Karlovu 2 Prague Czech Republic 12808 public
Citazione:
L. Dvorakova et al., "Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acidexchange", HUM MUTAT, 18(1), 2001, pp. 52-60

Abstract

X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta -oxidation. We examined the ABCD1 gene in probands from11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffectivein the restoration of defective beta -oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchangein the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be veri rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/Tin the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively. Hum Mutat 18:52-60, 2001, (C) 2001 Wiley-Liss. Inc.

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Documento generato il 04/04/20 alle ore 21:52:22