Abstract
We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperature gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789delTTAC) and a recurrent nonsense mutation, which was identified in two unrelated patients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nonsense mutation and the 4 bp deletion are both predicted to lead to a truncated protein product lacking the Cterminal 20% (aproximately) of its sequence. The occurrence of three independent mutations among 92 NF1 patients at codons 2263–2264 (exon 37) suggests that a specific search for mutations in this area should be undertaken in screening programs for NF1 mutations.
References
Abernathy CR, Colman SD, Kousseff BG, Wallace MR (1994) Two NF1 mutations: frameshift in the GAP-related domain, and loss of two codons toward the 3′ end of the gene. Hum Mutat 3:347–352
Ainsworth PJ, Rodenhiser DI (1991) Rapid nonradioactive detection by PCR of pHHH202/RsaI RFLP linked to neurofibromatosis type 1. Am J Hum Genet 49:1098–1099
Ainsworth PJ, Rodenhiser DI, Costa MT (1993) Identification and characterization of sporadic and inherited mutations in exon 31 of the neurofibromatosis (NF1) gene. Hum Genet 91:151–156
Andersen LB, Fountain JW, Gutmann DH, Tarlé SA, Glover TW, Dracopoli NC, Housman DE, Collin FS (1993) Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. Nature Genet 3:118–121
Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O'Connell P, White R (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell62:193–201
Costes B, Girodon E, Ghanem N, Chassignol M, Thuong NT, Dupret D, Goossens M (1993) Psoralen-modified oligonucleotide primers improve detection of mutations by denaturing gradient gel electrophoresis and provide an alternative to GC-clamping. Hum Mol Genet 2:393–397
Estivill X, Lázaro C, Casals T, Ravella A (1991) Recurrence of a nonsense mutation in the NF1 gene causing classical neurofibromatosis type 1. Hum Genet 88:185–188
Grompe M (1993) The rapid detection of unknown mutations in nucleic acids. Nature Genet 5:111–117
Horiuchi T, Hatta N, Matsumoto M, Ohtsuka H, Collins FS, Kobayashi Y, Fujita S (1994) Nonsense mutations at Arg-1947 in two cases of familial neurofibromatosis type 1 in Japanese. Hum Genet 93:81–83
Krawczak M, Cooper DN (1991) Gene deletions causing human disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet 86:425–441
Krawczak M, Cooper DN (1993) Human gene mutation. Bios, Oxford
Lázaro C, Gaona A, Xu G, Weiss R, Estivill X (1993) A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene. Hum Genet 92:429–430
Lázaro C, Goana A, Estivill X (1994) Two CA/GT repeat polymorphisms in intron 27 of the neurofibromatosis type 1 (NF1) gene. Hum Genet 93:351–352
Legius E, Marchuk DA, Collins FS, Glover TW (1993) Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumor suppressor gene hypothesis. Nature Genet 3:122–126
Lerman LS, Silverstein K (1987) Computational simulation of DNA melting and its application to denaturing gradient gel electrophoresis. Methods Enzymol 155:482–501
Li Y, Bollag G, Clark R, Stevens J, Conroy L, Fults D, Ward K, Friedman E, Samowitz W, Robertson M, Bradley P, Mc-Cormick F, White R, Cawthon R (1992) Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell 69:275–281
Marchuk DA, Saulino AM, Tavakkol R, Swaroop M, Wallace MR, Andersen LB, Mitchell AL, Gutmann DH, Boguski M, Collins FS (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11:931–940
Martin GA, Viskochill D, Bollag G, McCabe PC, Crosier WJ, Haubruck H, Conroy L, Clark R, O'Connell P, Cawthon RM, Innis MA, McCormick F (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 63:843–849
National Institutes of Health Consensus Development Conference (1988) Neurofibromatosis. Conference Statement. Arch Neurol45:575–578
Riccardi VM (1992) Neurofibromatosis: phenotype, natural history, and pathogenesis, 2nd edn. Johns Hopkins University Press, Baltimore
Shen MH, Harper PS, Upadhyaya M (1993) Neurofibromatosis type l (NF1): the search for mutations by PCR-heteroduplex analysis on Hydrolink gels. Hum Mol Genet 2:1861–1864
Stark M, Assum G, Krone W (1991) A small deletion and an adjacent base exchange in a potential stem-loop region of the neurofibromatosis type 1 gene. Hum Genet 87:685–687
Upadhyaya M, Shen M, Cherryson A, Farnham J, Maynard J, Huson SM, Harper PS (1992) Analysis of mutations at the neurofibromatosis 1 (NF1) locus. Hum Mol Genet 1:735–740
Valero MC, Velasco E, Moreno F, Hernandéz-Chico C (1994) Characterization of four mutations in the neurofibromatosis type 1 gene by denaturing gradient gel electrophoresis (DGGE) Hum Mol Genet 3:639–641
Xu G, Lin B, Tanaka K, Dunn D, Wood D, Gesteland R, White R, Weiss R, Tamanoi F (1990) The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 63:835–841
Xu G, Nelson L, O'Connell P, White R (1991) An Alu polymorphism intragenic to the NF1 gene. Nucleic Acids Res 19:3764
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Robinson, P.N., Böddrich, A., Peters, H. et al. Two recurrent nonsense mutations and a 4 bp deletion in a quasi-symmetric element in exon 37 of the NF1 gene. Hum Genet 96, 95–98 (1995). https://doi.org/10.1007/BF00214193
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DOI: https://doi.org/10.1007/BF00214193