Abstract
Neurofibromatosis type 1 (NF1) of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. We have scanned 14 different exons from the first part of the NF1 gene using the RNA-single strand conformation polymorphism (RNA-SSCP) method in a series of 40 NF1 patients. Three novel mutations, two nonsense and one missense, and two polymorphisms have been detected in familial cases. Genotype-phenotype correlations have been investigated, but no particular association has been detected. After this screening, the majority of NF1 chromosomes has not yet been characterized, confirming the difficulty in detecting the defect underlying NF1 in most families, even following extensive DNA analysis.
Similar content being viewed by others
References
Bisceglia L, Grifa A, Zelante L, Gasparini P (1994) Development of RNA-SSCP protocols for the identification and screening of CFTR mutations: identification of two new mutations. Hum Mutat 4: 136–140
Cawthon R, Weiss R, Xu G, Viskochil D, CulverM, Stephens 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
Crossey PA, Richards F, Foster K, Green J, Prowse A, Latif F, Lermann M, Zbar B, Affara N, Fergusson-Smith M, Maher E (1994) Identification of intragenic mutations in the von HippelLindau disease tumour suppressor gene and correlation with disease phenotype. Hum Mol Genet 3: 1303–1308
Easton D, Ponder M, Huson S, Ponder B (1993) An analysis of variation in expression of neurofibromatosis (NF) type I (NF1): evidence for modifying genes. Am J Hum Genet 53: 305–313
Gasparini P, Bonizzato A, Dognini M, Pignatti PF (1992) Restriction site generating-polymerase chain reaction (RG-PCR) for the probeless detection of hidden genetic variation: application to the study of some common cystic fibrosis mutations. Mol Cell Probes 6: 1–7
Gasparini P, Grifa A, Origone P, Coviello D, Antonacci R, Rocchi M (1993) Detection of a neurofibromatosis type 1 (NFl) homologous sequence by PCR: implications for the diagnosis and screening of genetic diseases. Mol Cell Probes 7: 415–418
Grifa A, Piemontese M, Melchionda S, Origone P, Zelante L, Coviello D, Fratta G, Dallapiccola B, Balestrazzi P, Ajmar F, Gasparini P (1995) Screening of neurofibromatosis type I gene: identification of a large deletion and of an intronic variant. Clin Genet 47:281–284
Heim R, Kam-Morgan L, Binnie C, Corns D, Cayouette M, Farber R, Aylsworth A, Silverman S, Luce M (1995) Distribution of 13 truncating mutations in the neurofibromatosis 1 gene. Hum Mol Genet 4:975–981
Huson SM, Compston D, Clarke P, Harper P (1989) A genetic study of von Recklinghausen neurofibromatosis in south-east Wales. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 26: 704–711
Huson SM, Hughes RAC (eds) (1994) The neurofibromatosis. A pathogenetic and clinical overview. Chapman & Hall, London
Korf BR (1995) Fax transmission of the NNFF international NF1 genetic analysis consortium, August 1995
Legius E, Marchuk D, Hall B, Andersen L, Wallace M, Collins F, Glover T (1992) NF-1 related locus on chromosome 15. Genomics 13: 1316–1318
Li Y, O'Connel P, Breidenbach H, Cawthon R, Stevens J, Xu G, Neil S, Robertson M, White R, Viskochil D (1995) Genomic organization of the neurofibromatosis 1 gene (NFI). Genomcs 25: 9–18
MacCollin M, Ramesh V, Jacoby L, Louis D, Rubio M, Pulaski K, Trofatter J, Short M, Bove C, Eldrige R, Parry D, Gusella J (1994) Mutational analysis of patients with neurofibromatosis 2. Am J Hum Genet 55: 314–320
Nishi T, Lee P, Oka K, Levi V, Tanase S, Morino Y, Saya M (1991) Differential expression of two types of the neurofibromatosis type 1 (NFI) gene transcripts related to neuronal differentiation. Oncogene 6: 1555–1559
Powell S, Peterson G, Krush A, Booker J, Jen J, Giardiello F, Hamilton S, Vogelstein B, Kinzler K (1993) Molecular diagnosis of familial adenomatous polyposis. N Engl J Med 329: 1982–1987
Sarkar G, Yoon H-S, Sommer S (1992) Screening for mutations by RNA single-strand conformation polymorphism (rSSCP): comparison with DNA-SSCP. Nucleic Acids Res 20: 871–878
Seizinger B (1993) NF1: a prevalent cause of tumorigenesis in human cancers? Nat Genet 3:97–99
Shattuck-Eidens D, et al (1995) A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. JAMA 273: 535–541
Suzuki Y, Suzuki H, Kaymana T, Yoshimoto T, Shibahara S (1991) Brain tumors predominantly express the neurofibromatosis type 1 gene transcripts containing the 63 base insert in the region coding for GTPase activating protein-related domain. Biochem Biophys Res Commun 187: 984–990
Upadhyaya M, Shaw D, Harper P (1994) Molecular basis of neurofibromatosis type l(NF1): mutation analysis and polymorphisms in the NFl gene. Hum Mutat 4:83–101
Viskochil D, Buchberg A, Xu G, Cawthon R, Stevens J, Wolff R, Culver M, Carey J, Copeland N, Jenkins N, 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, Marchuck D, Andersen L, Letcher R, Oden H, Sulino A, Fountain J, Brereton A, Nicholson J, Mitchell A, Brownstein B, Collins F (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181–186
Xu G, O'Connell, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R, Weiss R (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62: 599–608
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gasparini, P., D'Agruma, L., de Cillis, G.P. et al. Scanning the first part of the neurofibromatosis type 1 gene by RNA-SSCP: Identification of three novel mutations and of two new polymorphisms. Hum Genet 97, 492–495 (1996). https://doi.org/10.1007/BF02267073
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02267073