Exonic deletions in the NF1 gene in patients with neurofibromatosis type I from the lower Silesian region of Poland.

Background: Neurofibromatosis type I (NF1, Recklinghausen's disease) is an autosomal dominant disorder characterized by the following clinical features: café au lait spots, neurofibromas, Lisch nodules, freckling of the axillary and inguinal regions, optic nerve gliomas, bone dysplasia and increased risk of certain tumors. NF1 is diagnosed on the basis of clinical criteria, while identifying the genetic background of the disease is important mainly for genetic counseling. NF1 genetic analysis is based on searching for NF1 exon deletions/duplications using Multiplex ligation-dependent probe amplification (MLPA), searching for microdeletions of the critical region using fluorescence in situ hybridization (FISH), searching for point mutations by gene sequencing (in most cases) and analyzing mRNA.

Objectives: The aim of this study was to estimate the frequency of single and multi-exon deletions/duplications in the NF1 gene in Polish patients, and to evaluate the usefulness of MLPA as a cheap and easy method for NF1 molecular diagnosis, despite the fact that such changes may be found in only a small group of NF1 patients.

Material And Methods: The study included 65 patients suspected of NF1 or with recognized NF1 on the basis of clinical criteria. Cytogenetic analysis were carried out for all the patients, and for one patient with a translocation [46,XY,t(17;22)(q11.2;q11.2)], a FISH analysis was performed. All patients were tested for deletions/duplications in the NF1 gene using two MLPA kits for neurofibromatosis I.

Results: The MLPA analysis showed deletions in the NF1 gene in 7.7% of the cases (5/65).

Conclusions: The results indicate that an MLPA analysis may be performed in patients with a clinical diagnosis of NF1 or patients with suspected NF1 as an easy and inexpensive first molecular test, enabling the exclusion of about 7% of NF1 patients from expensive and time-consuming molecular diagnosis by DNA sequencing.