Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant disorder, occurring in 1 in 3,000-4,000 people1. It is a characterised by neurofibromas, café-au-lait spots, freckles, Lisch nodules, bone deformities, learning disabilities, macrocephaly, short stature and predisposition to developing tumours such as myeloid malignancies, gliomas and pheochromocytomas2,3,4.
NF1 is caused by mutations of the tumour suppressor gene, Neurofibromin 1 (NF1), which spans approximately 280kb and is located at 17q11.245. Mutations encompass both single nucleotide substitutions and large genomic deletions. Patients with deletions of the entire gene typically have a more severe presentation than those with intragenic mutations6. Approximately 5-20% of patients with NF1 carry a heterozygous deletion and thus lack one copy of the NF1 gene and further 11 or more contiguous genes7. There are two common sized recurrent deletions, both mediated by non-allelic homologous recombination between regions of high sequence homology: Type 1, spanning 1.4Mb between segmental duplicons and Type 2, with breakpoints in the SUZ12 gene and its pseudogene 1.2Mb away8. Atypical deletions have also been noted with non-recurrent breakpoints8.
1. Laycock-van Spyk S et al., Human Genomics 2011; 5:623-690
2. Bader JL et al., Ann N J Acad Sci 1986;486:57-65
3. Huson SM and Hughes RAC, The Neurofibromatoses: A Pathogenic and Clinical Overview. Chapman and Hall,London. 1994
4. Trovo-Marqui AB, Tajara EH et al., Clin Genet 2006;70:1-13
5. Cichowski K, Jacks T et al., Cell 2001;104(4):593-604
6. Pasmant E et al., Hum Mutat. 2010 Jun;31(6):E1506-18
7. Jeong SY et al., J Korean Med Sci. 2010 May;25(5):804-8
8. Steinmann et al., Eur J Hum Genet 2008;16:572-580
This product is intended to be used on Carnoy’s solution (3:1 methanol/acetic acid) fixed peripheral blood samples.