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. 1993 Jul;53(1):90–95.

Tandem duplication within a neurofibromatosis type 1 (NF1) gene exon in a family with features of Watson syndrome and Noonan syndrome.

M Tassabehji 1, T Strachan 1, M Sharland 1, A Colley 1, D Donnai 1, R Harris 1, N Thakker 1
PMCID: PMC1682238  PMID: 8317503

Abstract

Type 1 neurofibromatosis (NF1), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or that phenotypes arise from mutations in very closely linked genes. Here we provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication of 42 bases in exon 28 of the NF1 gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product.

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Selected References

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

  1. Abuelo D. N., Meryash D. L. Neurofibromatosis with fully expressed Noonan syndrome. Am J Med Genet. 1988 Apr;29(4):937–941. doi: 10.1002/ajmg.1320290426. [DOI] [PubMed] [Google Scholar]
  2. Allanson J. E., Hall J. G., Van Allen M. I. Noonan phenotype associated with neurofibromatosis. Am J Med Genet. 1985 Jul;21(3):457–462. doi: 10.1002/ajmg.1320210307. [DOI] [PubMed] [Google Scholar]
  3. Allanson J. E. Noonan syndrome. J Med Genet. 1987 Jan;24(1):9–13. doi: 10.1136/jmg.24.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allanson J. E., Upadhyaya M., Watson G. H., Partington M., MacKenzie A., Lahey D., MacLeod H., Sarfarazi M., Broadhead W., Harper P. S. Watson syndrome: is it a subtype of type 1 neurofibromatosis? J Med Genet. 1991 Nov;28(11):752–756. doi: 10.1136/jmg.28.11.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ballester R., Marchuk D., Boguski M., Saulino A., Letcher R., Wigler M., Collins F. The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell. 1990 Nov 16;63(4):851–859. doi: 10.1016/0092-8674(90)90151-4. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fountain J. W., Wallace M. R., Bruce M. A., Seizinger B. R., Menon A. G., Gusella J. F., Michels V. V., Schmidt M. A., Dewald G. W., Collins F. S. Physical mapping of a translocation breakpoint in neurofibromatosis. Science. 1989 Jun 2;244(4908):1085–1087. doi: 10.1126/science.2543076. [DOI] [PubMed] [Google Scholar]
  8. Huson S. M., Harper P. S., Compston D. A. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain. 1988 Dec;111(Pt 6):1355–1381. doi: 10.1093/brain/111.6.1355. [DOI] [PubMed] [Google Scholar]
  9. Ledbetter D. H., Rich D. C., O'Connell P., Leppert M., Carey J. C. Precise localization of NF1 to 17q11.2 by balanced translocation. Am J Hum Genet. 1989 Jan;44(1):20–24. [PMC free article] [PubMed] [Google Scholar]
  10. Li Y., Bollag G., Clark R., Stevens J., Conroy L., Fults D., Ward K., Friedman E., Samowitz W., Robertson M. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell. 1992 Apr 17;69(2):275–281. doi: 10.1016/0092-8674(92)90408-5. [DOI] [PubMed] [Google Scholar]
  11. Marchuk D. A., Saulino A. M., Tavakkol R., Swaroop M., Wallace M. R., Andersen L. B., Mitchell A. L., Gutmann D. H., Boguski M., Collins F. S. cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics. 1991 Dec;11(4):931–940. doi: 10.1016/0888-7543(91)90017-9. [DOI] [PubMed] [Google Scholar]
  12. Meinecke P. Evidence that the "neurofibromatosis-Noonan syndrome" is a variant of von Recklinghausen neurofibromatosis. Am J Med Genet. 1987 Mar;26(3):741–745. doi: 10.1002/ajmg.1320260331. [DOI] [PubMed] [Google Scholar]
  13. Menon A. G., Ledbetter D. H., Rich D. C., Seizinger B. R., Rouleau G. A., Michels V. F., Schmidt M. A., Dewald G., DallaTorre C. M., Haines J. L. Characterization of a translocation within the von Recklinghausen neurofibromatosis region of chromosome 17. Genomics. 1989 Aug;5(2):245–249. doi: 10.1016/0888-7543(89)90053-0. [DOI] [PubMed] [Google Scholar]
  14. Opitz J. M., Weaver D. D. The neurofibromatosis-Noonan syndrome. Am J Med Genet. 1985 Jul;21(3):477–490. doi: 10.1002/ajmg.1320210310. [DOI] [PubMed] [Google Scholar]
  15. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  16. Quattrin T., McPherson E., Putnam T. Vertical transmission of the neurofibromatosis/Noonan syndrome. Am J Med Genet. 1987 Mar;26(3):645–649. doi: 10.1002/ajmg.1320260320. [DOI] [PubMed] [Google Scholar]
  17. 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. 1991 Oct;87(6):685–687. doi: 10.1007/BF00201726. [DOI] [PubMed] [Google Scholar]
  18. Stern H. J., Saal H. M., Lee J. S., Fain P. R., Goldgar D. E., Rosenbaum K. N., Barker D. F. Clinical variability of type 1 neurofibromatosis: is there a neurofibromatosis-Noonan syndrome? J Med Genet. 1992 Mar;29(3):184–187. doi: 10.1136/jmg.29.3.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tassabehji M., Read A. P., Newton V. E., Harris R., Balling R., Gruss P., Strachan T. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature. 1992 Feb 13;355(6361):635–636. doi: 10.1038/355635a0. [DOI] [PubMed] [Google Scholar]
  20. Tiller G. E., Rimoin D. L., Murray L. W., Cohn D. H. Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia. Proc Natl Acad Sci U S A. 1990 May;87(10):3889–3893. doi: 10.1073/pnas.87.10.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Upadhyaya M., Cheryson A., Broadhead W., Fryer A., Shaw D. J., Huson S., Wallace M. R., Andersen L. B., Marchuk D. A., Viskochil D. A 90 kb DNA deletion associated with neurofibromatosis type 1. J Med Genet. 1990 Dec;27(12):738–741. doi: 10.1136/jmg.27.12.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Upadhyaya M., Shen M., Cherryson A., Farnham J., Maynard J., Huson S. M., Harper P. S. Analysis of mutations at the neurofibromatosis 1 (NF1) locus. Hum Mol Genet. 1992 Dec;1(9):735–740. doi: 10.1093/hmg/1.9.735. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Wallace M. R., Andersen L. B., Saulino A. M., Gregory P. E., Glover T. W., Collins F. S. A de novo Alu insertion results in neurofibromatosis type 1. Nature. 1991 Oct 31;353(6347):864–866. doi: 10.1038/353864a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Watson G. H. Pulmonary stenosis, café-au-lait spots, and dull intelligence. Arch Dis Child. 1967 Jun;42(223):303–307. doi: 10.1136/adc.42.223.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]

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