Diagnosi molecolare nella neurofibromatosi tipo 1

Translated title of the contribution: Molecular diagnosis in neurofibromatosis type 1

E. Bonioli, S. Costabel, A. Di Stefano, C. La Rosa, A. Citana, S. Massa, D. Coviello, F. Ajmar, P. Origone

Research output: Contribution to journalArticlepeer-review


Type 1 Neurofibromatosis is a frequent autosomal dominant disorder occurring approximately 1 in 3000 live births. The mutation rate is very high and approximately 50% of the patients are sporadic cases. NF1 is solely diagnosed on the basis of its clinical features which include cafè-au-lait spots, axillary and inguinal freckling, peripheral neurofibromas and Lisch nodules. A wide range of other complications can occur in NF1 patients, including plexiform neurofibromas, optic and chiasma gliomas, learning disabilities, scoliosis, pseudarthrosis and malignancy. Molecular analysis of NF1 gene is quite complex due to its large size (350 Kb) and to the heterogeneity of the mutations described. A protein truncation assay (PTT) has recently been developed, which allows the detection of approximately 50% of germline mutations in the gene. In our study we detected 18 truncated fragments indicating abnormal polypeptide in heterozygous condition, and 14 of these have been fully characterised by direct sequencing. We have diagnosed six mutations (C2041T, A2428T, C3816T, C4084T, C5380T, C5839T) three small deletions (2674delA, 7190-91delCT, 7331delA), four small insertions (1021-22insTT, 2027insC, 4106insTA, 7149insC) and one A-> C mutation in splice accepting site of intron 13. The extreme variability of the phenotypic expression of NF1 gene makes reproductive decisions in NF1 families very difficult, as molecular diagnosis cannot predict clinical expression of the disease. We have performed four prenatal diagnosis. In three cases the linkage analysis was carried out using informative markers. Direct approach using Protein Truncation Test and sequencing was performed in one case, in which a R1947X mutation was identified. Our experience confirms an evenly distribution of NF1 mutations over the entire coding region.

Translated title of the contributionMolecular diagnosis in neurofibromatosis type 1
Original languageItalian
Pages (from-to)35-39
Number of pages5
Issue number1
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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