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Three different premature stop codons lead to skipping of exon 7 in neurofibromatosis type I patients
Author(s) -
Wimmer Katharina,
Eckart Markus,
Stadler Peter F.,
Rehder Helga,
Fonatsch Christa
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200007)16:1<90::aid-humu20>3.0.co;2-j
Subject(s) - exon , biology , genetics , neurofibromatosis , gene , mutation , exon skipping , stop codon , frameshift mutation , allele , microbiology and biotechnology , alternative splicing
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder affecting one in 3,500 individuals. The mutation rate in the NF1 gene is one of the highest known for human genes. Compared to other methods, the protein truncation test (PTT) provides improved efficiency in detecting NF1 mutations which are dispersed throughout the gene which spans 350 kilobases of genomic DNA. We have applied the PTT and subsequent sequence analysis of cloned cDNA to identify mutations in NF1 patients. We report here the identification of two novel (W336X and Q315X), and one recurrent (R304X) mutation located in exon 7 and show that all three premature termination codons lead to skipping of exon 7 in a proportion of the transcripts derived from the mutated allele. Possible mutation‐induced alterations of the RNA secondary structure and their impact on skipping of exon 7 of the NF1 gene are explored and discussed. Hum Mutat 16:90–91, 2000. © Wiley‐Liss, Inc.