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. 1983 Feb;20(1):1–11. doi: 10.1136/jmg.20.1.1

The genetic status of mothers of isolated cases of Duchenne muscular dystrophy.

R J Lane, M Robinow, A D Roses
PMCID: PMC1048978  PMID: 6842530

Abstract

Classical genetic theory, based on assumed equal mutation rates in males and females, predicts that one-third of all cases of Duchenne muscular dystrophy (DMD) in a generation are born as new mutants to non-carrier mothers. Furthermore, less than half the mothers of apparently isolated cases appear to be carriers on the basis of raised serum creatine kinase levels. We have analysed the pedigrees of 61 families of DMD boys seen in the Duke Neuromuscular Research Clinic and 45 DMD families followed at the University of Virginia. The frequency of affected boys among the next born male sibs of 37 initially isolated DMD cases in two clinic populations was significantly greater than predicted by Haldane's theory (p = 0.029) and the estimated proportion of new mutant cases in the combined clinic population of 106 families was 0.127 (SE 0.111). The absence of affected males in earlier generations in families of isolated cases may be explained in part by a high ratio of male to female stillbirths and infant deaths, which was more than three times that of the normal population in this study. These data suggest that new mutant cases are less common than expected and current predictions may underestimate genetic risks in mothers of isolated cases.

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Selected References

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

  1. BLYTH H., PUGH R. J. Muscular dystrophy in childhood; the genetic aspect; a field study in the Leeds region of clinical types and their inheritance. Ann Hum Genet. 1959 Apr;23(2):127–163. doi: 10.1111/j.1469-1809.1958.tb01457.x. [DOI] [PubMed] [Google Scholar]
  2. Biggs R., Rizza C. R. The sporadic case of haemophilia A. Lancet. 1976 Aug 28;2(7983):431–433. doi: 10.1016/s0140-6736(76)92523-x. [DOI] [PubMed] [Google Scholar]
  3. Brooks A. P., Emery A. E. The incidence of Duchenne muscular dystrophy in the South East of Scotland. Clin Genet. 1977 Apr;11(4):290–294. doi: 10.1111/j.1399-0004.1977.tb01315.x. [DOI] [PubMed] [Google Scholar]
  4. Bucher K., Ionasescu V., Hanson J. Frequency of new mutants among boys with Duchenne muscular dystrophy. Am J Med Genet. 1980;7(1):27–34. doi: 10.1002/ajmg.1320070107. [DOI] [PubMed] [Google Scholar]
  5. Bundey S. Calculation of genetic risks in Duchenne muscular dystrophy by geneticists in the United Kingdom. J Med Genet. 1978 Aug;15(4):249–253. doi: 10.1136/jmg.15.4.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHEESEMAN E. A., KILPATRICK S. J., STEVENSON A. C., SMITH C. A. The sex ratio of mutation rates of sex-linked recessive genes in man with particular reference to Duchenne type muscular dystrophy. Ann Hum Genet. 1958 May;22(3):235–243. doi: 10.1111/j.1469-1809.1958.tb01418.x. [DOI] [PubMed] [Google Scholar]
  7. Caskey C. T., Nussbaum R. L., Cohan L. C., Pollack L. Sporadic occurrence of Duchenne muscular dystrophy: evidence for new mutation. Clin Genet. 1980 Nov;18(5):329–341. doi: 10.1111/j.1399-0004.1980.tb02293.x. [DOI] [PubMed] [Google Scholar]
  8. Cowan J., Macdessi J., Stark A., Morgan G. Incidence of Duchenne muscular dystrophy in New South Wales and Australian Capital Territory. J Med Genet. 1980 Aug;17(4):245–249. doi: 10.1136/jmg.17.4.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Danieli G. A., Mostacciuolo M. L., Pilotto G., Angelini C., Bonfante A. Duchenne muscular dystrophy: data from family studies. Hum Genet. 1980;54(1):63–68. doi: 10.1007/BF00279050. [DOI] [PubMed] [Google Scholar]
  10. Drummond L. M. Creatine phosphokinase levels in the newborn and their use in screening for Duchenne muscular dystrophy. Arch Dis Child. 1979 May;54(5):362–366. doi: 10.1136/adc.54.5.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Emery A. E., Holloway S. Use of normal daughters' and sisters' creatine kinase levels in estimating heterozygosity in Duchenne muscular dystrophy. Hum Hered. 1977;27(2):118–126. doi: 10.1159/000152860. [DOI] [PubMed] [Google Scholar]
  12. Emery A. E., Morton R. Genetic counselling in lethal X-linked disorders. Acta Genet Stat Med. 1968;18(6):534–542. doi: 10.1159/000152177. [DOI] [PubMed] [Google Scholar]
  13. Francke U., Felsenstein J., Gartler S. M., Migeon B. R., Dancis J., Seegmiller J. E., Bakay F., Nyhan W. L. The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease. Am J Hum Genet. 1976 Mar;28(2):123–137. [PMC free article] [PubMed] [Google Scholar]
  14. Gardner-Medwin D. Mutation rate in Duchenne type of muscular dystrophy. J Med Genet. 1970 Dec;7(4):334–337. doi: 10.1136/jmg.7.4.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Graham J. B. Genotype assignment (carrier detection) in the haemophilias. Clin Haematol. 1979 Feb;8(1):115–145. [PubMed] [Google Scholar]
  16. HALDANE J. B. Mutation in the sex-linked recessive type of muscular dystrophy; a possible sex difference. Ann Hum Genet. 1956 May;20(4):344–347. doi: 10.1111/j.1469-1809.1955.tb01289.x. [DOI] [PubMed] [Google Scholar]
  17. Ho A. D., Reitter B., Stojakowits S., Fiehn W., Weisser J. Capping of lymphocytes for carrier detection in Duchenne muscular dystrophy: technical problems and a review of the literature. Eur J Pediatr. 1980 Sep;134(3):211–216. doi: 10.1007/BF00441475. [DOI] [PubMed] [Google Scholar]
  18. Lane R. J., Gardner-Medwin D., Roses A. D. Electrocardiographic abnormalities in carriers of Duchenne muscular dystrophy. Neurology. 1980 May;30(5):497–501. doi: 10.1212/wnl.30.5.497. [DOI] [PubMed] [Google Scholar]
  19. Lange K., Gladstien K., Zatz M. Effects of reproductive compensation and genetic drift on X-linked lethals. Am J Hum Genet. 1978 Mar;30(2):180–189. [PMC free article] [PubMed] [Google Scholar]
  20. Lawrence E. F., Brown B., Hopkins I. J. Pseudohypertrophic muscular dystrophy of childhood: an epidemiological survey in Victoria. Aust N Z J Med. 1973 Apr;3(2):142–151. doi: 10.1111/j.1445-5994.1973.tb03967.x. [DOI] [PubMed] [Google Scholar]
  21. MORTON N. E., CHUNG C. S. Formal genetics of muscular dystrophy. Am J Hum Genet. 1959 Dec;11:360–379. [PMC free article] [PubMed] [Google Scholar]
  22. MOSER H., WIESMANN U., RICHTERICH R., ROSSI E. PROGRESSIVE MUSKELDYSTROPHIE. VI. HAEUFIGKEIT, KLINIK UND GENETIK DER DUCHENNE-FORM. Schweiz Med Wochenschr. 1964 Nov 14;94:1610–1621. [PubMed] [Google Scholar]
  23. Mabry M. E., Roses A. D. Increased [32P]-phosphorylation of tryptic peptides of erythrocyte spectrin in Duchenne muscular dystrophy. Muscle Nerve. 1981 Nov-Dec;4(6):489–493. doi: 10.1002/mus.880040605. [DOI] [PubMed] [Google Scholar]
  24. Meltzer H. Y., Dorus E., Grunhaus L., Davis J. M., Belmaker R. Genetic control of human plasma creatine phosphokinase activity. Clin Genet. 1978 Apr;13(4):321–326. doi: 10.1111/j.1399-0004.1978.tb01187.x. [DOI] [PubMed] [Google Scholar]
  25. Nicholson G. A., Lane R. J., Gardner-Medwin D., Walton J. N. Carrier testing in families of isolated cases of duchenne muscular dystrophy. Creatine kinase activities in female relatives of mothers with normal CK activity. J Neurol Sci. 1981 Jul;51(1):29–42. doi: 10.1016/0022-510x(81)90057-5. [DOI] [PubMed] [Google Scholar]
  26. Pickard N. A., Gruemer H. D., Verrill H. L., Isaacs E. R., Robinow M., Nance W. E., Myers E. C., Goldsmith B. Systemic membrane defect in the proximal muscular dystrophies. N Engl J Med. 1978 Oct 19;299(16):841–846. doi: 10.1056/NEJM197810192991601. [DOI] [PubMed] [Google Scholar]
  27. Prot J. Genetic-epidemiological studies in progressive muscular dystrophy. J Med Genet. 1971 Mar;8(1):90–95. doi: 10.1136/jmg.8.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Radu H., Migea S., Török Z., Bordeianu L., Radu A. Carrier detection in X-linked Duchenne type muscular dystrophy. A pluridimensional investigation. J Neurol Sci. 1968 Mar-Apr;6(2):289–300. doi: 10.1016/0022-510x(68)90097-x. [DOI] [PubMed] [Google Scholar]
  29. Roses A. D., Nicholson G. A., Roe C. R. Screening for Duchenne muscular dystrophy. Pediatrics. 1977 Aug;60(2):248–251. [PubMed] [Google Scholar]
  30. Roses A. D., Roses M. J., Metcalf B. S., Hull K. L., Nicholson G. A., Hartwig G. B., Roe C. R. Pedigree testing in Duchenne muscular dystrophy. Ann Neurol. 1977 Oct;2(4):271–278. doi: 10.1002/ana.410020403. [DOI] [PubMed] [Google Scholar]
  31. Roses A. D., Roses M. J., Miller S. E., Hull K. L., Jr, Appel S. H. Carrier detection in Duchenne muscular dystrophy. N Engl J Med. 1976 Jan 22;294(4):193–198. doi: 10.1056/NEJM197601222940404. [DOI] [PubMed] [Google Scholar]
  32. Roses A. D., Shile P. E., Herbstreith M. H., Balakrishnan C. V. Identification of abnormally [32P]-phosphorylated cyanogen bromide cleavage product of erythrocyte membrane spectrin in Duchenne muscular dystrophy. Neurology. 1981 Aug;31(8):1026–1030. doi: 10.1212/wnl.31.8.1026. [DOI] [PubMed] [Google Scholar]
  33. Roses M. S., Nicholson M. T., Kircher C. S., Roses A. D. Evaluation and detection of Duchenne's and Becker's muscular dystrophy carriers by manual muscle testing. Neurology. 1977 Jan;27(1):20–25. doi: 10.1212/wnl.27.1.20. [DOI] [PubMed] [Google Scholar]
  34. STEPHENS F. E., TYLER F. H. Studies in disorders of muscle. V. The inheritance of childhood progressive muscular dystrophy in 33 kindreds. Am J Hum Genet. 1951 Jun;3(2):111–125. [PMC free article] [PubMed] [Google Scholar]
  35. STEVENSON A. C. Muscular dystrophy in Northern Ireland, I. An account of the condition in fifty-one families. Ann Eugen. 1953 Jun;18(1):50–contd. doi: 10.1111/j.1469-1809.1952.tb02497.x. [DOI] [PubMed] [Google Scholar]
  36. STEVENSON A. C. Muscular dystrophy in Northern Ireland. IV. Some additional data. Ann Hum Genet. 1958 May;22(3):231–234. doi: 10.1111/j.1469-1809.1958.tb01417.x. [DOI] [PubMed] [Google Scholar]
  37. Sibert J. R., Harper P. S., Thompson R. J., Newcombe R. G. Carrier detection in Duchenne muscular dystrophy. Evidence from a study of obligatory carriers and mothers of isolated cases. Arch Dis Child. 1979 Jul;54(7):534–537. doi: 10.1136/adc.54.7.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Skolnick M., Carmelli D. A two-locus selection hypothesis for Duchenne muscular dystrophy. Theor Popul Biol. 1977 Oct;12(2):230–245. doi: 10.1016/0040-5809(77)90043-0. [DOI] [PubMed] [Google Scholar]
  39. Templeton A. R., Yokoyama S. Effect of reproductive compensation and the desire to have male offspring on the incidence of a sex-linked lethal disease. Am J Hum Genet. 1980 Jul;32(4):575–581. [PMC free article] [PubMed] [Google Scholar]
  40. Thompson M. W., Murphy E. G., McAlpine P. J. An assessment of the creatine kinase test in the detection of carriers of Duchenne muscular dystrophy. J Pediatr. 1967 Jul;71(1):82–93. doi: 10.1016/s0022-3476(67)80235-x. [DOI] [PubMed] [Google Scholar]
  41. Vogel F. A probable sex difference in some mutation rates. Am J Hum Genet. 1977 May;29(3):312–319. [PMC free article] [PubMed] [Google Scholar]
  42. Vogel F., Rathenberg R. Spontaneous mutation in man. Adv Hum Genet. 1975;5:223–318. doi: 10.1007/978-1-4615-9068-2_4. [DOI] [PubMed] [Google Scholar]
  43. WALTON J. N., RACE R. R., PHILIP U. On the inheritance of muscular dystrophy; with a note on the blood groups, and a note on colour vision and linkage studies. Ann Hum Genet. 1955 Aug;20(1):1–38. doi: 10.1111/j.1469-1809.1955.tb01274.x. [DOI] [PubMed] [Google Scholar]
  44. Yasuda N., Kondô K. No sex difference in mutations rates of Duchenne muscular dystrophy. J Med Genet. 1980 Apr;17(2):106–111. doi: 10.1136/jmg.17.2.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zatz M., Frota-Pessoa O., Levy J. A., Peres C. A. Creatine-phosphokinase (CPK) activity in relatives of patients with X-linked muscular dystrophies: a Brazilian study. J Genet Hum. 1976 Jun;24(2):153–168. [PubMed] [Google Scholar]
  46. Zellweger H., Antonik A. Newborn screening for Duchenne muscular dystrophy. Pediatrics. 1975 Jan;55(1):30–34. [PubMed] [Google Scholar]

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