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Article: Novel insertion 496_497insG creating a stop codon D194X in a Chinese family with X-Linked adrenoleukodystrophy

TitleNovel insertion 496_497insG creating a stop codon D194X in a Chinese family with X-Linked adrenoleukodystrophy
Authors
KeywordsABCD1 gene
Addison's disease, idiopathic
Adrenoleukodystrophy
Insertion
Mutation
X-linked adrenoleukodystrophy
Issue Date2005
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/HRE
Citation
Hormone Research, 2005, v. 63 n. 1, p. 1-5 How to Cite?
AbstractX-linked adrenoleukodystrophy (XALD, MIM 300100), the commonest inherited peroxisomal disorder, is characterized by central nervous system demyelination, primary adrenal failure and the systemic accumulation of saturated very long chain fatty acids (VLCFAs). The defective gene ABCD1 encodes an ATP-binding cassette (ABC) transport protein named ALDP, which functions as a crucial transporter of VLCFAs into the peroxisomes for β-oxidation. Here, we report a Chinese man with adrenomyeloneuropathy characterized by Addison's disease and spastic paraparesis. His plasma VLCFA levels, ratios of C24:0/C22:0 and C26:0/C22:0 were all significantly elevated. We performed mutation analysis of the ABCD1 gene in the proband and the family members using direct DNA sequencing and restriction analysis. A novel insertion 496_497insG in exon 1 causing a frame shift and a premature stop codon at amino acid position 194 (D194X) was identified (GenBank accession No. NM_000033). The insertional mutation abolishes an HhaI restriction site. The same mutation was found in his mother and the eldest sister even though their clinical and biochemical abnormalities were milder. Diagnosis of XALD often relies upon the detection of elevated VLCFA levels and ratios of C26:0/C22:0 and C24:0/C22:0 in fasting blood, however, 5-15% of the obligate heterozygotes would give normal values. DNA-based testing thus remains the most reliable tool for heterozygote detection when the disease-causing mutations are known. Using restriction fragment length polymorphism with HhaI, we have devised a rapid method for the identification of the carriers among the proband's family members and possibly for the screening of the mutations in other XALD patients. Copyright © 2005 S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/162781
ISSN
2011 Impact Factor: 2.48
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMak, CMen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorMa, OCen_HK
dc.contributor.authorTso, AWKen_HK
dc.contributor.authorTam, Sen_HK
dc.date.accessioned2012-09-05T05:23:27Z-
dc.date.available2012-09-05T05:23:27Z-
dc.date.issued2005en_HK
dc.identifier.citationHormone Research, 2005, v. 63 n. 1, p. 1-5en_HK
dc.identifier.issn0301-0163en_HK
dc.identifier.urihttp://hdl.handle.net/10722/162781-
dc.description.abstractX-linked adrenoleukodystrophy (XALD, MIM 300100), the commonest inherited peroxisomal disorder, is characterized by central nervous system demyelination, primary adrenal failure and the systemic accumulation of saturated very long chain fatty acids (VLCFAs). The defective gene ABCD1 encodes an ATP-binding cassette (ABC) transport protein named ALDP, which functions as a crucial transporter of VLCFAs into the peroxisomes for β-oxidation. Here, we report a Chinese man with adrenomyeloneuropathy characterized by Addison's disease and spastic paraparesis. His plasma VLCFA levels, ratios of C24:0/C22:0 and C26:0/C22:0 were all significantly elevated. We performed mutation analysis of the ABCD1 gene in the proband and the family members using direct DNA sequencing and restriction analysis. A novel insertion 496_497insG in exon 1 causing a frame shift and a premature stop codon at amino acid position 194 (D194X) was identified (GenBank accession No. NM_000033). The insertional mutation abolishes an HhaI restriction site. The same mutation was found in his mother and the eldest sister even though their clinical and biochemical abnormalities were milder. Diagnosis of XALD often relies upon the detection of elevated VLCFA levels and ratios of C26:0/C22:0 and C24:0/C22:0 in fasting blood, however, 5-15% of the obligate heterozygotes would give normal values. DNA-based testing thus remains the most reliable tool for heterozygote detection when the disease-causing mutations are known. Using restriction fragment length polymorphism with HhaI, we have devised a rapid method for the identification of the carriers among the proband's family members and possibly for the screening of the mutations in other XALD patients. Copyright © 2005 S. Karger AG, Basel.en_HK
dc.languageengen_US
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/HREen_HK
dc.relation.ispartofHormone Researchen_HK
dc.rightsHormone Research. Copyright © S Karger AG.-
dc.subjectABCD1 geneen_HK
dc.subjectAddison's disease, idiopathicen_HK
dc.subjectAdrenoleukodystrophyen_HK
dc.subjectInsertionen_HK
dc.subjectMutationen_HK
dc.subjectX-linked adrenoleukodystrophyen_HK
dc.subject.meshAtp-Binding Cassette Transporters - Genetics - Metabolismen_US
dc.subject.meshAdrenoleukodystrophy - Geneticsen_US
dc.subject.meshAdulten_US
dc.subject.meshAllelesen_US
dc.subject.meshChinaen_US
dc.subject.meshCodon, Terminator - Geneticsen_US
dc.subject.meshDna Transposable Elements - Geneticsen_US
dc.subject.meshFatty Acids - Metabolismen_US
dc.subject.meshFrameshift Mutationen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPolymorphism, Restriction Fragment Lengthen_US
dc.titleNovel insertion 496_497insG creating a stop codon D194X in a Chinese family with X-Linked adrenoleukodystrophyen_HK
dc.typeArticleen_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailTso, AWK: awk.tso@gmail.comen_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityTso, AWK=rp00535en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1159/000082319en_HK
dc.identifier.pmid15564782-
dc.identifier.scopuseid_2-s2.0-12544258592en_HK
dc.identifier.hkuros98200-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-12544258592&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume63en_HK
dc.identifier.issue1en_HK
dc.identifier.spage1en_HK
dc.identifier.epage5en_HK
dc.identifier.isiWOS:000226412400001-
dc.publisher.placeSwitzerlanden_HK
dc.identifier.scopusauthoridMak, CM=34971727200en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridMa, OC=7004452841en_HK
dc.identifier.scopusauthoridTso, AWK=6701371436en_HK
dc.identifier.scopusauthoridTam, S=7202037323en_HK

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