It has been found to interact with p21ras 17 and GTP, and is thought to prevent uncontrolled cell proliferation by converting active RasGTP to inactive RasGDP. 16 The GAP related domain (GRD) is the only known functional domain of the NF1 gene and spans exons 20–27a (bases 3497–4661). 13– 15 A 360 amino acid region of the predicted protein product shows homology with the GTPase activating (GAP) family of proteins in yeast and mammals. 12 The most common transcript codes for a polypeptide of 2818 amino acids called neurofibromin. The NF1 gene transcribes several mRNAs in the size range 11–13 kb expressed in neurones, oligodendrocytes and non-myelinating Schwann cells. 9– 11 It harbours at least three other embedded genes-EV12A, EV12B, and ONGP-transcribed from the opposite strand of NF1 intron 27b. 8 It spans a region of about 350 kb of genomic DNA and contains 60 exons. The NF1 gene maps to chromosome 17q11.2 and is thought to be a tumour suppressor gene because loss of heterozygosity is associated with the occurrence of benign and malignant tumours in tissues derived from the neural crest 5– 7 as well as myeloid malignancies. As a consequence genetic testing would have a major impact on the diagnosis and management of these families. In addition a number of patients who have a clinical picture suspected to be NF1 do not fulfil the diagnostic criteria particularly in the younger age groups. 2– 4 There is, however, great intra and interfamilial phenotypic variability. 1 Further manifestations are known to occur in this disorder, including macrocephaly, short stature, learning difficulties, scoliosis and certain malignancies. Most disease features are present in more than 90% of patients at puberty. Strict diagnostic criteria that include café au lait spots, neurofibromas, plexiform neurofibromas, freckling in the axillary or inguinal regions, Lisch nodules (iris haematomas), optic or chiasma glioma, pseudoarthrosis, and sphenoid dysplasia define NF1. It is a fully penetrant autosomal dominant disorder. Neurofibromatosis type 1 (NF1), formerly known as Von Recklinghausen Neurofibromatosis, is a common genetic disorder affecting approximately 1 in 3000–5000 people. ACSA, automated comparative sequence analysis.
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