LETTER TO JMG

Identification of a mutation that perturbs NF1 agene splicing using genomic DNA samples and a minigene assay

M Baralle¹, D Baralle^2,3, L De Conti¹, C Mattocks², J Whittaker², A Knezevich¹, C ffrench-Constant^2,3, F E Baralle¹

¹ International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, Trieste, Italy
² Department of Medical Genetics, Addenbrooke’s Hospital, Cambridge, UK
³ Department of Pathology, University of Cambridge, Cambridge, UK

Correspondence to:
Correspondence to:
Dr D Baralle, Department of Medical Genetics, Addenbrooke’s Hospital, Box 134, Hills Road, Cambridge CB2 2QQ, UK;
db314@cam.ac.uk

Keywords: NF1; splicing; minigene; pre-mRNA

The first 150 words of the full text of this article appear below.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disease. In recent studies on the neurofibromatosis type 1 (NF1) gene neurofibromin, splicing abnormalities were seen in 30-50% of cases when RNA taken from cell lines was analysed.^1,2 Unlike mutations that alter critical amino acids or generate premature stop codons, splicing abnormalities can be very hard to predict from sequence analysis alone. Apart from the two base pairs 5' and 3' of each exon, few of the nucleotides in regions critical for splicing are absolutely conserved. As a consequence, it can be very difficult to conclude that a sequence variation found in a patient will alter splicing and so represents a pathogenic mutation.

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