Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects
Autore:
Messiaen, LM; Callens, T; Mortier, G; Beysen, D; Vandenbroucke, I; Van Roy, N; Speleman, F; De Paepe, A;
Indirizzi:
State Univ Ghent Hosp, Ctr Med Genet, B-9000 Ghent, Belgium State Univ Ghent Hosp Ghent Belgium B-9000 Genet, B-9000 Ghent, Belgium
Titolo Testata:
HUMAN MUTATION
fascicolo: 6, volume: 15, anno: 2000,
pagine: 541 - 555
SICI:
1059-7794(2000)15:6<541:EMAOTN>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROFIBROMATOSIS TYPE-1 GENE; NONSENSE MUTATIONS; SEQUENCE; TUMORS; CHROMOSOME-17; TRANSCRIPTS; DISORDERS; DELETIONS; JUNCTIONS; EXON-37;
Keywords:
neurofibromatosis type 1; NF1; mutational spectrum; splicing errors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Messiaen, LM State Univ Ghent Hosp, Ctr Med Genet, De Pintelaan 185, B-9000 Ghent, Belgium State Univ Ghent Hosp De Pintelaan 185 Ghent Belgium B-9000
Citazione:
L.M. Messiaen et al., "Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects", HUM MUTAT, 15(6), 2000, pp. 541-555

Abstract

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders and is caused by mutations in the NF1 gene. Mutation detection is complex due to the large size of the NF1 gene, the presence of pseudogenes and the great variety of possible lesions. Although there is no evidencefor locus heterogeneity in NF1, mutation detection rates rarely exceed 50%. We studied 67 unrelated NF1 patients fulfilling the NIH diagnostic criteria, 29 familial and 38 sporadic cases, using a cascade of complementary techniques. We performed a protein truncation test starting from puromycin-treated EBV cell lines and, if no mutation was found, continued with heteroduplex, FISH, Southern blot and cytogenetic analysis. We identified the germline mutation in 64 of 67 patients and 32 of the mutations are novel. This isthe highest mutation detection rate reported in a study of typical NF1 patients. All mutations were studied at the genomic and RNA level. The mutational spectrum consisted of 25 nonsense, 12 frameshift, 19 splice mutations, six missense and/or small in-frame deletions, one deletion of the entire NF1 gene, and a translocation t(14;17)(q32;q11.2). Our data suggest that exons 10a-10c and 37 are mutation-rich regions and that together with some recurrent mutations they may account for almost 30% of the mutations in classical NF1 patients. We found a high frequency of unusual splice mutations outside of the AG/GT 5' and 3' splice sites. As some of these mutations form stable transcripts, it remains possible that a truncated neurofibromin is formed. Hum Mutat 15:541-555, 2000. (C) 2000 Wiley Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 06:52:53