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A novel diagnostic method to detect truncated neurofibromin in neurofibromatosis 1
Author(s) -
Esposito Teresa,
Piluso Giulio,
Saracino Dario,
Uccello Rossella,
Schettino Carla,
Dato Clemente,
Capaldo Guglielmo,
Giugliano Teresa,
Varriale Bruno,
Paolisso Giuseppe,
Di Iorio Giuseppe,
Melone Mariarosa A. B.
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13396
Subject(s) - neurofibromin 1 , neurofibromatosis , genetics , mutation , biology , mutation testing , gene , cancer research , microbiology and biotechnology
Neurofibromatosis type 1 ( NF 1) is an autosomal dominant genetic condition caused by dominant loss‐of‐function mutations of the tumor suppressor gene NF 1 that encodes neurofibromin, a negative regulator of RAS activity. Mutation analysis of NF 1 located at 17q11.2 has been hampered by the large size of the gene, the high rate of new mutations, the lack of mutational clustering, and the presence of several homologous loci. To date, about 80% of the reported NF 1 mutations are predicted to result in protein truncation, but very few studies have correlated the causative NF 1 mutation with its effect at the protein level. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in a large cohort of unrelated subjects suspected of having NF 1, according to the NIH consensus criteria. Western blot analysis was carried out on protein extracts from patients' leukocytes to highlight the possible presence of altered neurofibromin as a result of mutations in NF 1 . Truncated neurofibromin was identified in 274/336 patients (81%), confirming the usefulness and reproducibility of the proposed diagnostic approach. Our methodology can be routinely applied in the diagnostic setting, thanks to its simplicity and reliability. Combined with molecular approaches, it may increase the accuracy and efficiency of NF 1 genetic testing.We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in patients fulfilling the clinical criteria for Neurofibromatosis 1. Western blot analysis identified truncated neurofibromin in 274/336 patients (81%). Our results indicate that the proposed technique is cheap and reliable, and could ideally be performed as a preliminary biochemical screening before molecular analysis of the NF1 gene.