Summary
A single-strand conformational polymorphism found in the DNA of a patient with neurofibromatosis 1 (NF1) was shown to be caused by a deletion of a CCACC or CACCT sequence and an adjacent transversion, located about 500 base pairs downstream from the region that codes for a functional domain of the NF1 gene product. This mutation could also be detected in the patient and in his affected daughter by heteroduplex analysis. The deletion removes the proximal half of a small potential stem-loop and interrupts the reading frame in exon 1. A severely truncated protein with a grossly altered carboxy terminus lacking one third of its sequence is expected to be formed from the mutant allele.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 63:851–859
Buchberg AM, Cleveland LS, Jenkins NA, Copeland NG (1990) Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway. Nature 347:291–294
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. Cell 62:193–201
Efstratiadis A, Posakony J, Maniatis T, Lawn RM, O'Connell C, Spritz RA, DeRiel JK, Forget BG, Weissmann SM, Bechl AE, Smithies O, Baralle FE, Shoulders CC, Proudfoot NJ (1980) The structure and evolution of the human β-globin gene family. Cell 21:653–668
Fountain JW, Wallace MR, Bruce MA, Seizinger BR, Menon AG, Gusella JF, Michels VV, Schmidt MA, Dewald GW, Collins FS (1989) Physical mapping of a translocation breakpoint in neurofibromatosis. Science 244:1085–1087
Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) (1990) PCR protocols: a guide to methods and applications. Academic Press. New York London
Keen J, Lester D, Inglehearn C, Curtis A, Bhattacharya S (1991) Rapid detectin of single base mismatches as heteroduplexes on hydrolink gels. Trends Genet 7:5
Martin GA, Viskochil D, Bollag G, McCabe PC, Crosier W, 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
Menon AG, Ledbetter DH, Rich DC, Seizinger BR, Rouleau GA, Michels VF, Schmidt MA, Dewald G, DallaTorre CM, Haines JL, Gusella JF (1980) Characterization of a translocation within the von Recklinghausen neurofibromatosis region of chromosome 17. Genomics 5:245–249
O'Connell P, Leach R, Cawthon RM, Culver M, Stevens J, Viskochil D, Fournier REK, Rich DC, Ledbetter DH, White R (1989) Two NF1 translocations map within a 600-kilobase segment of 17q11. 2. Science 244:1087–1088
Orita M, Suzuki Y, Sekiya T, Hayashi K (1989) Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5:874–879
Riccardi VM, Eichner JE (1986) Neurofibromatosis: phenotype, natural history, and pathogenesis. Johns Hopkins University Press, Baltimore
Rubenstein AE, Korf BR (1990) Neurofibromatosis: a handbook for patients, families, and health-care professionals. Thieme, Stuttgart New York
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci 74:5463–5467
Upadhyaya M, Chreyson A, Broadhead W, Fryer A, Shaw DJ, Huson S, Wallace MR, Andersen LB, Marchuk DA, Viskochil D, Black D, O'Connell P, Collins FS, Harper PS (1990) A 90 kb deletion associated with neurofibromatosis type 1. J Med Genet 27:738–741
Viskochil D, Buchberg AM, Xu G, Cawthon R, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG, Jenkins NA, White R, O'Connell P (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62:187–192
Wallace MR, Marchuk DA, Anderson LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL, Brownstein BH, Collins FS (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181–186
Xu G, O'Connell P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R, Weiss R (1990a) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608
Xu G, Lin B, Tanaka K, Dunn D, Wood D, Gesteland R, White R, Weiss R, Tamanoi T (1990b) The catalytic domain of the eurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 63:835–841
Yagle MK, Parruti G, Xu W, Ponder BAJ, Solomon E (1990) Genetic and physical map of the von Recklinghausen neurofibromatosis (NF1) region on chromosome 17. Proc Natl Acad Sci USA 87:7255–7259
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stark, M., Assum, G. & Krone, W. A small deletion and an adjacent base exchange in a potential stem-loop region of the neurofibromatosis 1 gene. Hum Genet 87, 685–687 (1991). https://doi.org/10.1007/BF00201726
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00201726