Deletions of NF1 gene and exons detected by multiplex ligation-dependent probe amplification.
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 >or=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 >or=1 NF1 exons accounted for approximately 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.
De Luca
A
A
IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
Bottillo
I
I
Dasdia
M C
MC
Morella
A
A
Lanari
V
V
Bernardini
L
L
Divona
L
L
Giustini
S
S
Sinibaldi
L
L
Novelli
A
A
Torrente
I
I
Schirinzi
A
A
Dallapiccola
B
B
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003199:Computer Systems; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012600:Scoliosis / Q000453:epidemiology / Q000235:genetics