Abstract
Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1) which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689) flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689) in the interphases analyzed and two signals (RP5-1002G3conRP5-92689) in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.
Highlights
Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1) which codifies the protein neurofibromin
Neurofibromatosis type 1 is one of the most frequent autosomal dominant genetic disorders (OMIM 613113), affecting 1 in 3000 to 5000 people. It is caused by loss-of-function mutations in a tumor suppressor gene (NF1) mapped at 17q11.2 which codifies the protein neurofibromin [1]
Duplication of repetitive sequences is a not a feature restricted to pseudogenes, but it was observed in NF1 gene by high resolution fluorescence in situ hybridization (FISH) [4]
Summary
Neurofibromatosis type 1 is one of the most frequent autosomal dominant genetic disorders (OMIM 613113), affecting 1 in 3000 to 5000 people. It is caused by loss-of-function mutations in a tumor suppressor gene (NF1) mapped at 17q11.2 which codifies the protein neurofibromin [1]. Pseudogenes located in 2q21, 14q11, and 22q11 present a high sequence homology It seems that a 640 kb fragment was originally duplicated in 2q21 and transposed to 14q11. We describe a case in which tandem duplications in NF1 gene were detected in a neurofibromatosis patient who presented a personal and familial history of compatible with a hereditary cancer syndrome, specially lymphoproliferative malignancies
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