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. 1997 Nov;34(11):907–911. doi: 10.1136/jmg.34.11.907

DNA testing for fragile X syndrome: implications for parents and family.

M A van Rijn 1, B B de Vries 1, A Tibben 1, A M van den Ouweland 1, D J Halley 1, M F Niermeijer 1
PMCID: PMC1051118  PMID: 9391884

Abstract

The fragile X syndrome is an X linked, semidominant mental retardation disorder caused by the amplification of a CGG repeat in the 5' UTR of the FMR1 gene. Nineteen fragile X families in which the mutated FMR1 gene segregated were evaluated. The implications of the diagnosis for the parents and family were studied through pedigree information, interviews, and questionnaires. Information about the heredity of fragile X syndrome was only disseminated by family members to a third (124/366) of the relatives with an a priori risk of being a carrier of the fragile X syndrome. Twenty-six percent (94/366) of the relatives were tested. Transmission of information among first degree relatives seemed satisfactory but dropped off sharply with increasing distance of the genetic relationship, leaving 66% uninformed. This is particularly disadvantageous in an X linked disease. Of those subjects tested, 42% (39/94) had a premutation and 18% (17/94) had a full mutation. On average, in each family one new fragile X patient and two new carriers were found. When people have the task of transmitting genetic information to their relatives, they usually feel responsible and capable; however, reduced acquaintance and contact with more distant relative severely reduces the effectiveness of such transfer of information in fragile X families.

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Selected References

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

  1. Ayme Ségolène, Macquart-Moulin Geneviève, Julian-Reynier Claire, Chabal Françoise, Giraud Francis. Diffusion of information about genetic risk within families. Neuromuscul Disord. 1993 Sep-Nov;3(5-6):571–574. doi: 10.1016/0960-8966(93)90118-4. [DOI] [PubMed] [Google Scholar]
  2. Beck A. T. Hopelessness as a predictor of eventual suicide. Ann N Y Acad Sci. 1986;487:90–96. doi: 10.1111/j.1749-6632.1986.tb27888.x. [DOI] [PubMed] [Google Scholar]
  3. Beck A. T., Weissman A., Lester D., Trexler L. The measurement of pessimism: the hopelessness scale. J Consult Clin Psychol. 1974 Dec;42(6):861–865. doi: 10.1037/h0037562. [DOI] [PubMed] [Google Scholar]
  4. Denayer L., De Boeck K., Evers-Kiebooms G., Van den Berghe H. The transfer of information about genetic transmission to brothers and sisters of parents with a CF-child. Birth Defects Orig Artic Ser. 1992;28(1):149–158. [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Fu Y. H., Kuhl D. P., Pizzuti A., Pieretti M., Sutcliffe J. S., Richards S., Verkerk A. J., Holden J. J., Fenwick R. G., Jr, Warren S. T. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991 Dec 20;67(6):1047–1058. doi: 10.1016/0092-8674(91)90283-5. [DOI] [PubMed] [Google Scholar]
  7. Horowitz M., Wilner N., Alvarez W. Impact of Event Scale: a measure of subjective stress. Psychosom Med. 1979 May;41(3):209–218. doi: 10.1097/00006842-197905000-00004. [DOI] [PubMed] [Google Scholar]
  8. McConkie-Rosell A., Robinson H., Wake S., Staley L. W., Heller K., Cronister A. Dissemination of genetic risk information to relatives in the fragile X syndrome: guidelines for genetic counselors. Am J Med Genet. 1995 Dec 4;59(4):426–430. doi: 10.1002/ajmg.1320590406. [DOI] [PubMed] [Google Scholar]
  9. Murray A., Youings S., Dennis N., Latsky L., Linehan P., McKechnie N., Macpherson J., Pound M., Jacobs P. Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers. Hum Mol Genet. 1996 Jun;5(6):727–735. doi: 10.1093/hmg/5.6.727. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Oostra B. A., Verkerk A. J. The fragile X syndrome: isolation of the FMR-1 gene and characterization of the fragile X mutation. Chromosoma. 1992 Apr;101(7):381–387. doi: 10.1007/BF00582832. [DOI] [PubMed] [Google Scholar]
  12. Rona R. J., Beech R., Mandalia S., Donnai D., Kingston H., Harris R., Wilson O., Axtell C., Swan A. V., Kavanagh F. The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing. Clin Genet. 1994 Aug;46(2):198–204. doi: 10.1111/j.1399-0004.1994.tb04224.x. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Surh L. C., Cappelli M., MacDonald N. E., Mettler G., Dales R. E. Cystic fibrosis carrier screening in a high-risk population. Participation based on a traditional recruitment process. Arch Pediatr Adolesc Med. 1994 Jun;148(6):632–637. doi: 10.1001/archpedi.1994.02170060086017. [DOI] [PubMed] [Google Scholar]
  16. Suslak L., Price D. M., Desposito F. Transmitting balanced translocation carrier information within families: a follow-up study. Am J Med Genet. 1985 Feb;20(2):227–232. doi: 10.1002/ajmg.1320200204. [DOI] [PubMed] [Google Scholar]
  17. Sutherland G. R., Ashforth P. L. X-linked mental retardation with macro-orchidism and the fragile site at Xq 27 or 28. Hum Genet. 1979 Apr 17;48(1):117–120. doi: 10.1007/BF00273283. [DOI] [PubMed] [Google Scholar]
  18. Turner G., Daniel A., Frost M. X-linked mental retardation, macro-orchidism, and the Xq27 fragile site. J Pediatr. 1980 May;96(5):837–841. doi: 10.1016/s0022-3476(80)80552-x. [DOI] [PubMed] [Google Scholar]
  19. Turner G., Robinson H., Laing S., Purvis-Smith S. Preventive screening for the fragile X syndrome. N Engl J Med. 1986 Sep 4;315(10):607–609. doi: 10.1056/NEJM198609043151002. [DOI] [PubMed] [Google Scholar]
  20. Turner G., Webb T., Wake S., Robinson H. Prevalence of fragile X syndrome. Am J Med Genet. 1996 Jul 12;64(1):196–197. doi: 10.1002/(SICI)1096-8628(19960712)64:1<196::AID-AJMG35>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  21. Varekamp I., Suurmeijer T., Bröcker-Vriends A., Rosendaal F. R. Hemophilia and the use of genetic counseling and carrier testing within family networks. Birth Defects Orig Artic Ser. 1992;28(1):139–148. [PubMed] [Google Scholar]
  22. 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]
  23. Wolff G., Back E., Arleth S., Rapp-Körner U. Genetic counseling in families with inherited balanced translocations: experience with 36 families. Clin Genet. 1989 Jun;35(6):404–416. doi: 10.1111/j.1399-0004.1989.tb02965.x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Zavodny P. J., Petro M. E., Kumar C. C., Dailey S. H., Lonial H. K., Narula S. K., Leibowitz P. J. The nucleotide sequence of chicken smooth muscle myosin light chain two. Nucleic Acids Res. 1988 Feb 11;16(3):1214–1214. doi: 10.1093/nar/16.3.1214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zigmond A. S., Snaith R. P. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x. [DOI] [PubMed] [Google Scholar]
  27. de Vries B. B., Wiegers A. M., Smits A. P., Mohkamsing S., Duivenvoorden H. J., Fryns J. P., Curfs L. M., Halley D. J., Oostra B. A., van den Ouweland A. M. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet. 1996 May;58(5):1025–1032. [PMC free article] [PubMed] [Google Scholar]

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