Article Text
Abstract
To estimate the contribution of single and multi-exon NF1 gene copy-number changes to the NF1 mutation spectrum, we analysed a series of 201 Italian patients with neurofibromatosis type 1 (NF1). Of these, 138 had previously been found, using denaturing high-performance liquid chromatography or protein truncation test, to be heterozygous for intragenic NF1 point mutations/deletions/insertions, and were excluded from this analysis. The remaining 63 patients were analysed using multiplex ligation-dependent probe amplification (MLPA), which allows detection of deletions or duplications encompassing ⩾1 NF1 exons, as well as entire gene deletions. MLPA results were validated using real-time quantitative PCR (qPCR) or fluorescent in situ hybridisation. MLPA screening followed by real-time qPCR detected a total of 23 deletions. Of these deletions, six were single exon, eight were multi-exon, and nine were of the entire NF1 gene. In our series, deletions encompassing ⩾1 NF1 exons accounted for ∼7% (14/201) of the NF1 gene mutation spectrum, suggesting that screening for these should now be systematically included in genetic testing of patients with NF1.
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Footnotes
Funding: This work was supported by the Italian Ministry of Health (Ricerca Corrente 2006–2007). A. De Luca is also supported by the Michael Smith Foundation for Health Research.
Competing interests: none declared.
- Abbreviations:
- CSRD
- cysteine-serine rich domain
- DHPLC
- denaturing high-performance liquid chromatography
- FISH
- fluorescence in situ hybridisation
- GAP
- GTPase-activating protein
- MLPA
- multiplex ligation-dependent probe amplification
- NIH
- National Institutes of Health
- NF1
- neurofibromatosis type 1
- OMIM
- Online Mendelian Inheritance in Man
- PTT
- protein truncation test
- qPCR
- quantitative PCR
- SSCP
- single-strand conformational polymorphism