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Titolo:
A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia
Autore:
Katsumata, N; Kawada, Y; Yamamoto, Y; Noda, M; Nimura, A; Horikawa, R; Tanaka, T;
Indirizzi:
Natl Childrens Med Res Ctr, Dept Endocrinol & Metab, Setagaya Ku, Tokyo 1548509, Japan Natl Childrens Med Res Ctr Tokyo Japan 1548509 Ku, Tokyo 1548509, Japan Univ Occupat & Environm Hlth, Dept Pediat, Kitakyushu, Fukuoka 8078555, Japan Univ Occupat & Environm Hlth Kitakyushu Fukuoka Japan 8078555 8555, Japan
Titolo Testata:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
fascicolo: 11, volume: 84, anno: 1999,
pagine: 3983 - 3987
SICI:
0021-972X(199911)84:11<3983:ANCHMI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIDE-CHAIN CLEAVAGE; STAR GENE; DNA; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Katsumata, N Natl Childrens Med Res Ctr, Dept Endocrinol & Metab, SetagayaKu, 3-35-31 Taishido, Tokyo 1548509, Japan Natl Childrens Med Res Ctr 3-35-31 Taishido Tokyo Japan 1548509
Citazione:
N. Katsumata et al., "A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia", J CLIN END, 84(11), 1999, pp. 3983-3987

Abstract

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. Recently, it was reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. In the present study, we have analyzed the StAR gene of a Japanese patient with CLAH. PCR amplification and subsequent nucleotide sequencing of the StAR gene and those of her parents revealed that the patient has a compound heterozygous mutation of this gene. In one allele, an undescribed G to C transversion in codon 217, which occurred at the last base of exon 5 and thus altered the splice donor site sequence, apparently resulted in a substitution of Arg to Thr (AGG to ACG: R217T), and in the other allele, a C to T transition in codon 218 causeda substitution of Ala to Val (GCG to GTG: A218V), which has been previously shown to abolish StAR activity. In vitro expression analysis of an allelic minigene that consists of exons 4-6 of the R217T mutant StAR gene showed that the G to C transversion in the splice donor site of exon 5 caused by the R217T mutation disrupts normal splicing, resulting in the complete skipping of exon 5, which alters the translation reading frame of exon 6, introduces a stop codon at amino acid position 174, and thus impairs the activity. A functional expression study of the R217T replacement mutant revealed that the mutant has no steroidogenesis-enhancing activity if the transcript of the R217T mutant allele is ever spliced normally and translated into the protein. From the genetic analysis of 50 healthy subjects, the novel R217T mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in theStAR gene (T217R and A218V) and that these mutations inactivate the StAR function and give rise to clinically manifest CLAH.

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Documento generato il 29/09/20 alle ore 19:43:33