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Titolo:
Comprehensive mutation analysis of TSC1 and TSC2 - and phenotypic correlations in 150 families with tuberous sclerosis
Autore:
Jones, AC; Shyamsundar, MM; Thomas, MW; Maynard, J; Idziaszczyk, S; Tomkins, S; Sampson, JR; Cheadle, JP;
Indirizzi:
Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales Univ Wales Coll Med Cardiff S Glam Wales CF4 4XN f CF4 4XN, S Glam, Wales
Titolo Testata:
AMERICAN JOURNAL OF HUMAN GENETICS
fascicolo: 5, volume: 64, anno: 1999,
pagine: 1305 - 1315
SICI:
0002-9297(199905)64:5<1305:CMAOTA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYCYSTIC KIDNEY-DISEASE; SPLICE-SITE MUTATION; GENE-2 PRODUCT; PROTEIN; IDENTIFICATION; DELETION; HETEROZYGOSITY; HAMARTIN; COMPLEX; DOMAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Sampson, JR Univ Wales Hosp, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales Univ Wales Hosp Cardiff S Glam Wales CF4 4XN N, S Glam, Wales
Citazione:
A.C. Jones et al., "Comprehensive mutation analysis of TSC1 and TSC2 - and phenotypic correlations in 150 families with tuberous sclerosis", AM J HU GEN, 64(5), 1999, pp. 1305-1315

Abstract

Tuberous sclerosis (TSC [MIM 191090 and MIM 191100]) is an autosomal dominant disorder characterized by hamartomas in many organs. Two thirds of cases are sporadic and are thought to represent new mutations. TSC is caused bymutations affecting either of the presumed tumor-suppressor genes, TSC1 and TSC2. Both appear to function as tumor suppressors, because somatic loss or intragenic mutation of the corresponding wild-type allele is seen in theassociated hamartomas. Here we report the first comprehensive mutation analysis of TSC1 and TSC2 in a cohort of 150 unrelated TSC patients and their families, using heteroduplex and SSCP analysis of all coding exons and using pulsed-field gel electrophoresis and conventional Southern blot analysis and long PCR to screen for large rearrangements. Mutations were characterized in 120 (80%) of the 150 cases, affecting TSC1 in 22 cases and TSC2 in 38cases. TSC1 mutations were significantly underrepresented in sporadic cases (P = .000185). Twenty-two patients had TSC2 missense mutations that were found predominantly in the GAP-related domain (eight cases) and in a small region encoded in exons 16 and 17, between nucleotides 1849 and 1859 (eightcases), consistent with the presence of residues performing key functions at these sites. In contrast, all TSC1 mutations were predicted to be truncating, consistent with a structural or adapter role for the encoded protein,Intellectual disability was significantly more frequent in TSC2 sporadic cases than in TSC1 sporadic cases (P = .0145). These data provide the first representative picture of the distribution and spectrum of mutations acrossthe TSC1 and TSC2 loci in clinically ascertained TSC and support a difference in severity of TSC1- and TSC2-associated disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 15:50:19