Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1991 Nov;28(11):746–751. doi: 10.1136/jmg.28.11.746

A genetic study of neurofibromatosis 1 in south-western Ontario. I. Population, familial segregation of phenotype, and molecular linkage.

D I Rodenhiser 1, M B Coulter-Mackie 1, J H Jung 1, S M Singh 1
PMCID: PMC1017109  PMID: 1685193

Abstract

This report is concerned with neurofibromatosis type 1 (NF-1, 17q11.2) in south-western Ontario, an ethnically diverse population derived from multiple immigrations. The population incidence, prevalence, and mutation rates for this disease are similar in most racial groups of this population and are also comparable to earlier reports. NF-1 is one of the most common single gene disorders in this population. The occurrence of the disease is not affected by the birth order or sex of the transmitting parent. The severe manifestation of this disease is statistically related to paternal transmission. Five polymorphic DNA probes (pA1041, pHHH202, pTH1719, NF1, pEW206, pEW207) were evaluated in relation to segregation of NF-1 using appropriate restriction enzymes. The observed heterozygosity was found to be relatively high, ranging from 25% to 55% for all the probes on 17q and flanking the NF-1 gene. We recommend the use of pHHH202/pTH1719 and pEW206 in any linkage analysis for detection of the presence of the NF-1 mutation. For informative families the degree of certainty is as high as 99.5%. Some future modifications may include the use of NF-1 exon specific probes and primers that remain to be evaluated for heterogeneity and heterozygosity among populations.

Full text

PDF
746

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BORBERG A. Clinical and genetic investigations into tuberous sclerosis and Recklinghausen's neurofibromatosis; contribution to elucidation of interrelationship and eugenics of the syndromes. Acta Psychiatr Neurol Scand Suppl. 1951;71:1–239. [PubMed] [Google Scholar]
  2. Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
  3. Collins F. S., O'Connell P., Ponder B. A., Seizinger B. R. Progress towards identifying the neurofibromatosis (NF1) gene. Trends Genet. 1989 Jul;5(7):217–221. doi: 10.1016/0168-9525(89)90085-1. [DOI] [PubMed] [Google Scholar]
  4. Collins F. S., Ponder B. A., Seizinger B. R., Epstein C. J. The von Recklinghausen neurofibromatosis region on chromosome 17--genetic and physical maps come into focus. Am J Hum Genet. 1989 Jan;44(1):1–5. [PMC free article] [PubMed] [Google Scholar]
  5. Elliott J., Coulter-Mackie M. B., Jung J. H., Rodenhiser D. I., Singh S. M. A method for transforming lymphocytes from very small blood volumes suitable for paediatric samples. Hum Genet. 1991 Apr;86(6):615–616. doi: 10.1007/BF00201551. [DOI] [PubMed] [Google Scholar]
  6. Giannelli F., Green P. M., High K. A., Lozier J. N., Lillicrap D. P., Ludwig M., Olek K., Reitsma P. H., Goossens M., Yoshioka A. Haemophilia B: database of point mutations and short additions and deletions. Nucleic Acids Res. 1990 Jul 25;18(14):4053–4059. doi: 10.1093/nar/18.14.4053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldgar D. E., Green P., Parry D. M., Mulvihill J. J. Multipoint linkage analysis in neurofibromatosis type I: an international collaboration. Am J Hum Genet. 1989 Jan;44(1):6–12. [PMC free article] [PubMed] [Google Scholar]
  8. Huson S. M., Compston D. A., Clark P., Harper P. S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989 Nov;26(11):704–711. doi: 10.1136/jmg.26.11.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jadayel D., Fain P., Upadhyaya M., Ponder M. A., Huson S. M., Carey J., Fryer A., Mathew C. G., Barker D. F., Ponder B. A. Paternal origin of new mutations in von Recklinghausen neurofibromatosis. Nature. 1990 Feb 8;343(6258):558–559. doi: 10.1038/343558a0. [DOI] [PubMed] [Google Scholar]
  10. Jeanpierre M. A rapid method for the purification of DNA from blood. Nucleic Acids Res. 1987 Nov 25;15(22):9611–9611. doi: 10.1093/nar/15.22.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miller M., Hall J. G. Possible maternal effect on severity of neurofibromatosis. Lancet. 1978 Nov 18;2(8099):1071–1073. doi: 10.1016/s0140-6736(78)91804-4. [DOI] [PubMed] [Google Scholar]
  12. O'Connell P., Leach R. J., Ledbetter D. H., Cawthon R. M., Culver M., Eldridge J. R., Frej A. K., Holm T. R., Wolff E., Thayer M. J. Fine structure DNA mapping studies of the chromosomal region harboring the genetic defect in neurofibromatosis type I. Am J Hum Genet. 1989 Jan;44(1):51–57. [PMC free article] [PubMed] [Google Scholar]
  13. Riccardi V. M., Dobson C. E., 2nd, Chakraborty R., Bontke C. The pathophysiology of neurofibromatosis: IX. Paternal age as a factor in the origin of new mutations. Am J Med Genet. 1984 May;18(1):169–176. doi: 10.1002/ajmg.1320180121. [DOI] [PubMed] [Google Scholar]
  14. Riccardi V. M., Kleiner B. Neurofibromatosis: a neoplastic birth defect with two age peaks of severe problems. Birth Defects Orig Artic Ser. 1977;13(3C):131–138. [PubMed] [Google Scholar]
  15. Riccardi V. M., Lewis R. A. Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants. Am J Hum Genet. 1988 Feb;42(2):284–289. [PMC free article] [PubMed] [Google Scholar]
  16. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  17. Sergeyev A. S. On the mutation rate of neurofibromatosis. Humangenetik. 1975 Jun 19;28(2):129–138. doi: 10.1007/BF00735745. [DOI] [PubMed] [Google Scholar]
  18. Upadhyaya M., Sarfarazi M., Huson S. M., Broadhead W., Fryer A., Harper P. S. Close flanking markers for neurofibromatosis type I (NF1). Am J Hum Genet. 1989 Jan;44(1):41–47. [PMC free article] [PubMed] [Google Scholar]
  19. Viskochil D., Buchberg A. M., Xu G., Cawthon R. M., Stevens J., Wolff R. K., Culver M., Carey J. C., Copeland N. G., Jenkins N. A. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 1990 Jul 13;62(1):187–192. doi: 10.1016/0092-8674(90)90252-a. [DOI] [PubMed] [Google Scholar]
  20. Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. doi: 10.1126/science.2134734. [DOI] [PubMed] [Google Scholar]
  21. Ward K., O'Connell P., Carey J. C., Leppert M., Jolley S., Plaetke R., Ogden B., White R. Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers. Am J Hum Genet. 1990 May;46(5):943–949. [PMC free article] [PubMed] [Google Scholar]
  22. Xu G. F., O'Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell. 1990 Aug 10;62(3):599–608. doi: 10.1016/0092-8674(90)90024-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES