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Titolo:
DETECTION AND FUNCTIONAL-CHARACTERIZATION OF THE NOVEL MISSENSE MUTATION Y254D IN TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASE (3-BETA-HSD) GENE OF A FEMALE-PATIENT WITH NONSALT-LOSING 3-BETA-HSD DEFICIENCY
Autore:
SANCHEZ R; RHEAUME E; LAFLAMME N; ROSENFIELD RL; LABRIE F; SIMARD J;
Indirizzi:
CHU LAVAL,RES CTR,MRC,MOLEC ENDOCRINOL GRP QUEBEC CITY G1V 4G2 PQ CANADA CHU LAVAL,RES CTR,MRC,MOLEC ENDOCRINOL GRP QUEBEC CITY G1V 4G2 PQ CANADA UNIV LAVAL QUEBEC CITY G1V 4G2 PQ CANADA UNIV CHICAGO,PRITZKER SCH MED,DEPT PEDIAT CHICAGO IL 60637
Titolo Testata:
The Journal of clinical endocrinology and metabolism
fascicolo: 3, volume: 78, anno: 1994,
pagine: 561 - 567
SICI:
0021-972X(1994)78:3<561:DAFOTN>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGENITAL ADRENAL-HYPERPLASIA; STEROID 21-HYDROXYLASE DEFICIENCY; DELTA-5-DELTA-4 ISOMERASE; PERIPHERAL-TISSUES; EXPRESSION; GONADS; LIVER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
R. Sanchez et al., "DETECTION AND FUNCTIONAL-CHARACTERIZATION OF THE NOVEL MISSENSE MUTATION Y254D IN TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASE (3-BETA-HSD) GENE OF A FEMALE-PATIENT WITH NONSALT-LOSING 3-BETA-HSD DEFICIENCY", The Journal of clinical endocrinology and metabolism, 78(3), 1994, pp. 561-567

Abstract

Three beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4-isomerase (3 beta HSD) deficiency is a form of congenital adrenal hyperplasia characterized by severe impairment of steroid biosynthesis in the adrenals and gonads. To better understand the molecular basis of the phenotypicheterogeneity found in 3 beta HSD deficiency, we analyzed the structure of type I and II 3 beta HSD genes in a female patient with nonsalt-losing 3 beta HSD deficiency diagnosed at puberty. We directly sequenced DNA fragments generated by polymerase chain reaction amplification of the four exons, the exon-intron boundaries, and the 5'-flanking regions of each gene. No mutation was detected in the type I 3 beta HSD gene, which is the predominant species expressed in the placenta and peripheral tissues. We detected a novel missense mutation, Y254D, in oneallele of the patient's type II 3 beta HSD gene, which is the almost exclusive type expressed in the adrenals and gonads. The influence of the Y254D mutation on enzymatic activity was assessed by analyzing therecombinant mutant enzyme generated by site-directed mutagenesis after its transient expression in COS-1 monkey kidney cells. Recombinant mutant type II S beta HSD enzyme carrying the Y254D substitution exhibits no detectable activity with C-21 Delta(5)-steroid pregnenolone or C-19 Delta(5)-steroid dehydroepiandrosterone used as substrate. The absence of restriction fragment length polymorphism by Southern blot analysis and the finding that all of the amplified DNA fragments possess the expected length suggest the absence of deletions, duplications, or rearrangements in the other allele. A putative second mutation could be located farther than 1427 basepairs upstream of the initiation codon, thus potentially affecting the normal expression of this gene or within intronic regions, generating an alternative aberrant splicing site. These are possibilities that remain to be elucidated. The present findings, which describe the novel missense mutation Y254D in the human type II 3 beta HSD gene, provide useful information on the structure-activity relationships of the 3 beta HSD superfamily.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 18:40:18