Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1996 May;33(5):376–378. doi: 10.1136/jmg.33.5.376

FMR1 fully expanded mutation with minimal methylation in a high functioning fragile X male.

Z Wang 1, A K Taylor 1, J A Bridge 1
PMCID: PMC1050605  PMID: 8733046

Abstract

Cytogenetic and molecular genetic analysis of a peripheral blood sample from a 31 year old, non-mentally retarded male with a family history of fragile X syndrome showed unexpected results. Nine percent of cells evaluated cytogenetically expressed a fragile X chromosome and molecular examination of the FMR1 gene showed a highly unusual pattern defined as a minimally methylated fully expanded mutation. This case illustrates the need to recognise exceptional variations of fragile X syndrome mutations.

Full text

PDF
376

Images in this article

377Image
on p.377

Selected References

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

  1. Bell M. V., Hirst M. C., Nakahori Y., MacKinnon R. N., Roche A., Flint T. J., Jacobs P. A., Tommerup N., Tranebjaerg L., Froster-Iskenius U. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell. 1991 Feb 22;64(4):861–866. doi: 10.1016/0092-8674(91)90514-y. [DOI] [PubMed] [Google Scholar]
  2. Gustavson K. H., Blomquist H. K., Holmgren G. Prevalence of the fragile-X syndrome in mentally retarded boys in a Swedish county. Am J Med Genet. 1986 Jan-Feb;23(1-2):581–587. doi: 10.1002/ajmg.1320230152. [DOI] [PubMed] [Google Scholar]
  3. Hagerman R. J., Hull C. E., Safanda J. F., Carpenter I., Staley L. W., O'Connor R. A., Seydel C., Mazzocco M. M., Snow K., Thibodeau S. N. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet. 1994 Jul 15;51(4):298–308. doi: 10.1002/ajmg.1320510404. [DOI] [PubMed] [Google Scholar]
  4. Kremer E. J., Pritchard M., Lynch M., Yu S., Holman K., Baker E., Warren S. T., Schlessinger D., Sutherland G. R., Richards R. I. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science. 1991 Jun 21;252(5013):1711–1714. doi: 10.1126/science.1675488. [DOI] [PubMed] [Google Scholar]
  5. Lubs H. A. A marker X chromosome. Am J Hum Genet. 1969 May;21(3):231–244. [PMC free article] [PubMed] [Google Scholar]
  6. Merenstein S. A., Shyu V., Sobesky W. E., Staley L., Berry-Kravis E., Nelson D. L., Lugenbeel K. A., Taylor A. K., Pennington B. F., Hagerman R. J. Fragile X syndrome in a normal IQ male with learning and emotional problems. J Am Acad Child Adolesc Psychiatry. 1994 Nov-Dec;33(9):1316–1321. doi: 10.1097/00004583-199411000-00014. [DOI] [PubMed] [Google Scholar]
  7. Oberlé I., Rousseau F., Heitz D., Kretz C., Devys D., Hanauer A., Boué J., Bertheas M. F., Mandel J. L. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science. 1991 May 24;252(5009):1097–1102. doi: 10.1126/science.252.5009.1097. [DOI] [PubMed] [Google Scholar]
  8. Reyniers E., Vits L., De Boulle K., Van Roy B., Van Velzen D., de Graaff E., Verkerk A. J., Jorens H. Z., Darby J. K., Oostra B. The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Nat Genet. 1993 Jun;4(2):143–146. doi: 10.1038/ng0693-143. [DOI] [PubMed] [Google Scholar]
  9. Rousseau F., Heitz D., Biancalana V., Blumenfeld S., Kretz C., Boué J., Tommerup N., Van Der Hagen C., DeLozier-Blanchet C., Croquette M. F. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med. 1991 Dec 12;325(24):1673–1681. doi: 10.1056/NEJM199112123252401. [DOI] [PubMed] [Google Scholar]
  10. Sherman S. L., Jacobs P. A., Morton N. E., Froster-Iskenius U., Howard-Peebles P. N., Nielsen K. B., Partington M. W., Sutherland G. R., Turner G., Watson M. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet. 1985;69(4):289–299. doi: 10.1007/BF00291644. [DOI] [PubMed] [Google Scholar]
  11. Taylor A. K., Safanda J. F., Fall M. Z., Quince C., Lang K. A., Hull C. E., Carpenter I., Staley L. W., Hagerman R. J. Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA. 1994 Feb 16;271(7):507–514. [PubMed] [Google Scholar]
  12. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  13. Webb T. P., Bundey S., Thake A., Todd J. The frequency of the fragile X chromosome among schoolchildren in Coventry. J Med Genet. 1986 Oct;23(5):396–399. doi: 10.1136/jmg.23.5.396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wöhrle D., Hennig I., Vogel W., Steinbach P. Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat Genet. 1993 Jun;4(2):140–142. doi: 10.1038/ng0693-140. [DOI] [PubMed] [Google Scholar]
  15. Yu S., Pritchard M., Kremer E., Lynch M., Nancarrow J., Baker E., Holman K., Mulley J. C., Warren S. T., Schlessinger D. Fragile X genotype characterized by an unstable region of DNA. Science. 1991 May 24;252(5009):1179–1181. doi: 10.1126/science.252.5009.1179. [DOI] [PubMed] [Google Scholar]

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

RESOURCES