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. 1989 Jan;44(1):20–24.

Precise localization of NF1 to 17q11.2 by balanced translocation.

D H Ledbetter 1, D C Rich 1, P O'Connell 1, M Leppert 1, J C Carey 1
PMCID: PMC1715462  PMID: 2491776

Abstract

A female patient is described with von Recklinghausen neurofibromatosis (NF1) in association with a balanced translocation between chromosome 17 and 22 [46,XX,t(17;22)(q11.2;q11.2)]. The breakpoint in chromosome 17 is cytogenetically identical to a previously reported case of NF1 associated with a 1;17 balanced translocation and suggests that the translocation events disrupt the NF1 gene. This precisely maps the NF1 gene to 17q11.2 and provides a physical reference point for strategies to clone the breakpoint and therefore the NF1 gene. A human-mouse somatic cell hybrid was constructed from patient lymphoblasts which retained the derivative chromosome 22 (22pter----22q11.2::17q11.2----17qter) but not the derivative 17q or normal 17. Southern blot analysis with genes and anonymous probes known to be in proximal 17q showed ErbA1, ErbB2, and granulocyte colony-stimulating factor (CSF3) to be present in the hybrid and therefore distal to the breakpoint, while pHHH202 (D17S33) and beta crystallin (CRYB1) were absent in the hybrid and therefore proximal to the breakpoint. The gene cluster including ErbA1 is known to be flanked by the constitutional 15;17 translocation breakpoint in hybrid SP3 and by the acute promyelocytic leukemia (APL) breakpoint, which provides the following gene and breakpoint order: cen-SP3-(D17S33,CRYB1)-NF1-(CSF3,ERBA1, ERBB2)-APL-tel. The flanking breakpoints of SP3 and API are therefore useful for rapidly localizing new markers to the neurofibromatosis critical region, while the breakpoints of the two translocation patients provide unique opportunities for reverse genetic strategies to clone the NF1 gene.

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Selected References

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

  1. Barker D., Wright E., Nguyen K., Cannon L., Fain P., Goldgar D., Bishop D. T., Carey J., Baty B., Kivlin J. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science. 1987 May 29;236(4805):1100–1102. doi: 10.1126/science.3107130. [DOI] [PubMed] [Google Scholar]
  2. Bloomfield C. D., Trent J. M., van den Berghe H. Report of the committee on structural chromosome changes in neoplasia. Cytogenet Cell Genet. 1987;46(1-4):344–366. doi: 10.1159/000132485. [DOI] [PubMed] [Google Scholar]
  3. Bodrug S. E., Ray P. N., Gonzalez I. L., Schmickel R. D., Sylvester J. E., Worton R. G. Molecular analysis of a constitutional X-autosome translocation in a female with muscular dystrophy. Science. 1987 Sep 25;237(4822):1620–1624. doi: 10.1126/science.3629260. [DOI] [PubMed] [Google Scholar]
  4. Boyd Y., Buckle V., Holt S., Munro E., Hunter D., Craig I. Muscular dystrophy in girls with X;autosome translocations. J Med Genet. 1986 Dec;23(6):484–490. doi: 10.1136/jmg.23.6.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boyd Y., Munro E., Ray P., Worton R., Monaco T., Kunkel L., Craig I. Molecular heterogeneity of translocations associated with muscular dystrophy. Clin Genet. 1987 Apr;31(4):265–272. doi: 10.1111/j.1399-0004.1987.tb02805.x. [DOI] [PubMed] [Google Scholar]
  6. Ferro M. T., San Román C. Constitutional t(15;17) Cancer Genet Cytogenet. 1981 Aug;4(1):89–91. doi: 10.1016/0165-4608(81)90011-x. [DOI] [PubMed] [Google Scholar]
  7. Fountain J. W., Wallace M. R., Brereton A. M., O'Connell P., White R. L., Rich D. C., Ledbetter D. H., Leach R. J., Fournier R. E., Menon A. G. Physical mapping of the von Recklinghausen neurofibromatosis region on chromosome 17. Am J Hum Genet. 1989 Jan;44(1):58–67. [PMC free article] [PubMed] [Google Scholar]
  8. Le Beau M. M., Rowley J. D., Ferro M. T., San Román C. Constitutional t(15;17): clarification of the chromosomal breakpoints. Cancer Genet Cytogenet. 1986 Feb 1;20(1-2):175–177. doi: 10.1016/0165-4608(86)90124-x. [DOI] [PubMed] [Google Scholar]
  9. Mitelman F., Manolov G., Manolova Y., Billström R., Heim S., Kristoffersson U., Mandahl N., Ferro M. T., San Roman C. High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2. Cancer Genet Cytogenet. 1986 Jun;22(2):95–98. doi: 10.1016/0165-4608(86)90168-8. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Seizinger B. R., Rouleau G. A., Ozelius L. J., Lane A. H., Faryniarz A. G., Chao M. V., Huson S., Korf B. R., Parry D. M., Pericak-Vance M. A. Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell. 1987 Jun 5;49(5):589–594. doi: 10.1016/0092-8674(87)90534-4. [DOI] [PubMed] [Google Scholar]
  12. Sheer D., Sheppard D. M., le Beau M., Rowley J. D., San Roman C., Solomon E. Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17. Ann Hum Genet. 1985 Jul;49(Pt 3):167–171. doi: 10.1111/j.1469-1809.1985.tb01690.x. [DOI] [PubMed] [Google Scholar]
  13. Skolnick M. H., Ponder B., Seizinger B. Linkage of NF1 to 12 chromosome 17 markers: a summary of eight concurrent reports. Genomics. 1987 Dec;1(4):382–383. doi: 10.1016/0888-7543(87)90043-7. [DOI] [PubMed] [Google Scholar]
  14. White R., Nakamura Y., O'Connell P., Leppert M., Lalouel J. M., Barker D., Goldgar D., Skolnick M., Carey J., Wallis C. E. Tightly linked markers for the neurofibromatosis type 1 gene. Genomics. 1987 Dec;1(4):364–367. doi: 10.1016/0888-7543(87)90040-1. [DOI] [PubMed] [Google Scholar]
  15. van Tuinen P., Rich D. C., Summers K. M., Ledbetter D. H. Regional mapping panel for human chromosome 17: application to neurofibromatosis type 1. Genomics. 1987 Dec;1(4):374–381. doi: 10.1016/0888-7543(87)90042-5. [DOI] [PubMed] [Google Scholar]

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