Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1995 Sep;32(9):689–691. doi: 10.1136/jmg.32.9.689

Influence of the sex of the transmitting grandparent in congenital myotonic dystrophy.

A López de Munain 1, A M Cobo 1, J J Poza 1, D Navarrete 1, L Martorell 1, F Palau 1, J I Emparanza 1, M Baiget 1
PMCID: PMC1051667  PMID: 8544186

Abstract

To analyse the influence of the sex of the transmitting grandparents on the occurrence of the congenital form of myotonic dystrophy (CDM), we have studied complete three generation pedigrees of 49 CDM cases, analysing: (1) the sex distribution in the grandparents' generation, and (2) the intergenerational amplification of the CTG repeat, measured in its absolute and relative values, between grandparents and the mothers of CDM patients and between the latter and their CDM children. The mean relative intergenerational increase in the 32 grandparent-mother pairs was significantly greater than in the 56 mother-CDM pairs (Mann-Whitney U test, p < 0.001). The mean expansion of the grandfathers (103 CTG repeats) was also significantly different from that seen in the grandmothers' group (154 CTG repeats) (Mann-Whitney U test, p < 0.01). This excess of non-manifesting males between the CDM grandparents' generation with a smaller CTG length than the grandmothers could suggest that the premutation has to be transmitted by a male to reach the degree of instability responsible for subsequent intergenerational CTG expansions without size constraints characteristic of the CDM range.

Full text

PDF
691

Selected References

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

  1. Ashizawa T., Dunne P. W., Ward P. A., Seltzer W. K., Richards C. S. Effects of the sex of myotonic dystrophy patients on the unstable triplet repeat in their affected offspring. Neurology. 1994 Jan;44(1):120–122. doi: 10.1212/wnl.44.1.120. [DOI] [PubMed] [Google Scholar]
  2. Aslanidis C., Jansen G., Amemiya C., Shutler G., Mahadevan M., Tsilfidis C., Chen C., Alleman J., Wormskamp N. G., Vooijs M. Cloning of the essential myotonic dystrophy region and mapping of the putative defect. Nature. 1992 Feb 6;355(6360):548–551. doi: 10.1038/355548a0. [DOI] [PubMed] [Google Scholar]
  3. Barceló J. M., Mahadevan M. S., Tsilfidis C., MacKenzie A. E., Korneluk R. G. Intergenerational stability of the myotonic dystrophy protomutation. Hum Mol Genet. 1993 Jun;2(6):705–709. doi: 10.1093/hmg/2.6.705. [DOI] [PubMed] [Google Scholar]
  4. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  5. Brunner H. G., Brüggenwirth H. T., Nillesen W., Jansen G., Hamel B. C., Hoppe R. L., de Die C. E., Höweler C. J., van Oost B. A., Wieringa B. Influence of sex of the transmitting parent as well as of parental allele size on the CTG expansion in myotonic dystrophy (DM). Am J Hum Genet. 1993 Nov;53(5):1016–1023. [PMC free article] [PubMed] [Google Scholar]
  6. Brunner H. G., Smeets H. J., Nillesen W., van Oost B. A., van den Biezenbos J. B., Joosten E. M., Pinckers A. J., Hamel B. C., Theeuwes A. G., Wieringa B. Myotonic dystrophy. Predictive value of normal results on clinical examination. Brain. 1991 Oct;114(Pt 5):2303–2311. doi: 10.1093/brain/114.5.2303. [DOI] [PubMed] [Google Scholar]
  7. Buxton J., Shelbourne P., Davies J., Jones C., Van Tongeren T., Aslanidis C., de Jong P., Jansen G., Anvret M., Riley B. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature. 1992 Feb 6;355(6360):547–548. doi: 10.1038/355547a0. [DOI] [PubMed] [Google Scholar]
  8. Cobo A. M., Baiget M., López de Munain A., Poza J. J., Emparanza J. I., Johnson K. Sex-related difference in intergenerational expansion of myotonic dystrophy gene. Lancet. 1993 May 1;341(8853):1159–1160. doi: 10.1016/0140-6736(93)93186-5. [DOI] [PubMed] [Google Scholar]
  9. Fu Y. H., Pizzuti A., Fenwick R. G., Jr, King J., Rajnarayan S., Dunne P. W., Dubel J., Nasser G. A., Ashizawa T., de Jong P. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256–1258. doi: 10.1126/science.1546326. [DOI] [PubMed] [Google Scholar]
  10. Harley H. G., Brook J. D., Rundle S. A., Crow S., Reardon W., Buckler A. J., Harper P. S., Housman D. E., Shaw D. J. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature. 1992 Feb 6;355(6360):545–546. doi: 10.1038/355545a0. [DOI] [PubMed] [Google Scholar]
  11. Harley H. G., Rundle S. A., MacMillan J. C., Myring J., Brook J. D., Crow S., Reardon W., Fenton I., Shaw D. J., Harper P. S. Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. Am J Hum Genet. 1993 Jun;52(6):1164–1174. [PMC free article] [PubMed] [Google Scholar]
  12. Jansen G., Willems P., Coerwinkel M., Nillesen W., Smeets H., Vits L., Höweler C., Brunner H., Wieringa B. Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J Hum Genet. 1994 Apr;54(4):575–585. [PMC free article] [PubMed] [Google Scholar]
  13. Koch M. C., Grimm T., Harley H. G., Harper P. S. Genetic risks for children of women with myotonic dystrophy. Am J Hum Genet. 1991 Jun;48(6):1084–1091. [PMC free article] [PubMed] [Google Scholar]
  14. Lavedan C., Hofmann-Radvanyi H., Rabes J. P., Roume J., Junien C. Different sex-dependent constraints in CTG length variation as explanation for congenital myotonic dystrophy. Lancet. 1993 Jan 23;341(8839):237–237. doi: 10.1016/0140-6736(93)90097-z. [DOI] [PubMed] [Google Scholar]
  15. Lavedan C., Hofmann-Radvanyi H., Shelbourne P., Rabes J. P., Duros C., Savoy D., Dehaupas I., Luce S., Johnson K., Junien C. Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am J Hum Genet. 1993 May;52(5):875–883. [PMC free article] [PubMed] [Google Scholar]
  16. Mahadevan M. S., Amemiya C., Jansen G., Sabourin L., Baird S., Neville C. E., Wormskamp N., Segers B., Batzer M., Lamerdin J. Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene. Hum Mol Genet. 1993 Mar;2(3):299–304. doi: 10.1093/hmg/2.3.299. [DOI] [PubMed] [Google Scholar]
  17. Mahadevan M., Tsilfidis C., Sabourin L., Shutler G., Amemiya C., Jansen G., Neville C., Narang M., Barceló J., O'Hoy K. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6;255(5049):1253–1255. doi: 10.1126/science.1546325. [DOI] [PubMed] [Google Scholar]
  18. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mulley J. C., Staples A., Donnelly A., Gedeon A. K., Hecht B. K., Nicholson G. A., Haan E. A., Sutherland G. R. Explanation for exclusive maternal origin for congenital form of myotonic dystrophy. Lancet. 1993 Jan 23;341(8839):236–237. doi: 10.1016/0140-6736(93)90096-y. [DOI] [PubMed] [Google Scholar]
  20. Nakagawa M., Yamada H., Higuchi I., Kaminishi Y., Miki T., Johnson K., Osame M. A case of paternally inherited congenital myotonic dystrophy. J Med Genet. 1994 May;31(5):397–400. doi: 10.1136/jmg.31.5.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohya K., Tachi N., Chiba S., Sato T., Kon S., Kikuchi K., Imamura S., Yamagata H., Miki T. Congenital myotonic dystrophy transmitted from an asymptomatic father with a DM-specific gene. Neurology. 1994 Oct;44(10):1958–1960. doi: 10.1212/wnl.44.10.1958. [DOI] [PubMed] [Google Scholar]
  22. Passos-Bueno M. R., Cerqueira A., Vainzof M., Marie S. K., Zatz M. Myotonic dystrophy: genetic, clinical, and molecular analysis of patients from 41 Brazilian families. J Med Genet. 1995 Jan;32(1):14–18. doi: 10.1136/jmg.32.1.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Redman J. B., Fenwick R. G., Jr, Fu Y. H., Pizzuti A., Caskey C. T. Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring. JAMA. 1993 Apr 21;269(15):1960–1965. [PubMed] [Google Scholar]

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

RESOURCES