Home LiteratureArticle Details
PMID: 1733826 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Parental origin and germline mosaicism of deletions and duplications of the dystrophin gene: a European study.

Human genetics ·Vol. 88 ·No. 3 ·1992-01-00 ·Pages 249-57

van Essen AJ, Abbs S, Baiget M, Bakker E, Boileau C, van Broeckhoven C, Bushby K, Clarke A, Claustres M, Covone AE

Abstract

Knowledge about the parental origin of new mutations and the occurrence of germline mosaicism is important for estimating recurrence risks in Duchenne (DMD) and Becker muscular dystrophy (BMD). However, there are problems in resolving these issues partly because not all mutations can as yet be directly detected, and additionally because genetic ratios are very sensitive to ascertainment bias. In the present study, therefore, analysis was restricted to currently detectable mutations (deletions and duplications) in particular types of families which tend to be rare. In order to obtain sufficient data we pooled results from 25 European centers. In mothers of affected patients who were the first in their family with a dystrophin gene deletion or duplication, the ratio between the paternal and the maternal origin of this new mutation was 32:49 (binomial test P = 0.075) for DMD. In five BMD families the ratio between paternal and maternal origin of new mutations was 3:2. Recurrence risk because of maternal germline mosaicism was studied in sisters or subsequent sibs of isolated cases with an apparently new detectable mutation. In 12 out of 59 (0.20; 95% CI 0.10-0.31) transmissions of the risk haplotype the DMD mutation was transmitted as well. No recurrences were found in nine BMD families.

MeSH Terms
Chromosome Deletion Dystrophin/genetics Female Genetic Carrier Screening Humans Male Mosaicism/genetics Multigene Family Muscular Dystrophies/genetics Mutation Pedigree
Chemicals
Dystrophin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
van Essen A J
Department of Medical Genetics, University of Groningen, The Netherlands.
Abbs S
Baiget M
Bakker E
Boileau C
van Broeckhoven C
Bushby K
Clarke A
Claustres M
Covone A E
References (51)
51 references, click to expand
  1. New mutations in Duchenne muscular dystrophy.
    Lancet. 1988 Oct 22;2(8617):971-2 PMID: 2902424
  2. Review and hypotheses: somatic mosaicism: observations related to clinical genetics.
    Am J Hum Genet. 1988 Oct;43(4):355-63 PMID: 3052049
  3. Prevalence and incidence of Becker muscular dystrophy.
    Lancet. 1991 Apr 27;337(8748):1022-4 PMID: 1673177
  4. The parental origin of mutations causing Duchenne muscular dystrophy.
    Arch Neurol. 1988 Jan;45(1):85-7 PMID: 3337681
  5. Evidence for mutation by unequal sister chromatid exchange in the Duchenne muscular dystrophy gene.
    Am J Hum Genet. 1989 Jun;44(6):855-63 PMID: 2567117
  6. Multipoint linkage analysis of the short arm of the human X chromosome in families with X-linked muscular dystrophy.
    Hum Genet. 1985;70(4):365-75 PMID: 3860471
  7. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.
    Am J Hum Genet. 1989 Oct;45(4):498-506 PMID: 2491009
  8. Origin of new mutations in Duchenne muscular dystrophy.
    Hum Genet. 1986 Dec;74(4):456-60 PMID: 2878873
  9. Prenatal diagnosis of Duchenne muscular dystrophy: a three-year experience in a rapidly evolving field.
    J Inherit Metab Dis. 1989;12 Suppl 1:174-90 PMID: 2509804
  10. Germinal mosaicism increases the recurrence risk for 'new' Duchenne muscular dystrophy mutations.
    J Med Genet. 1989 Sep;26(9):553-9 PMID: 2810338
  11. The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.
    Am J Hum Genet. 1976 Mar;28(2):123-37 PMID: 1266847
  12. Molecular deletion patterns in Duchenne and Becker type muscular dystrophy.
    Hum Genet. 1989 Mar;81(4):343-8 PMID: 2784778
  13. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene.
    Nature. 1986 Oct 16-22;323(6089):646-50 PMID: 3773991
  14. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals.
    Cell. 1987 Jul 31;50(3):509-17 PMID: 3607877
  15. Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion.
    Clin Genet. 1990 Aug;38(2):155-9 PMID: 2208768
  16. Sex ratio of the mutation frequencies in haemophilia A: coagulation assays and RFLP analysis.
    J Med Genet. 1991 Oct;28(10):672-80 PMID: 1682494
  17. Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases.
    Hum Genet. 1990 May;84(6):522-6 PMID: 2338336
  18. Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels.
    Nature. 1987 Oct 15-21;329(6140):640-2 PMID: 2889148
  19. Preferential deletion of exons in Duchenne and Becker muscular dystrophies.
    Nature. 1987 Oct 15-21;329(6140):638-40 PMID: 2821406
  20. Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus.
    Hum Genet. 1990 Oct;85(6):581-6 PMID: 2227948
  21. On the power to detect differences between male and female mutation rates for Duchenne muscular dystrophy, using classical segregation analysis and restriction fragment length polymorphisms.
    Am J Hum Genet. 1986 Jun;38(6):827-40 PMID: 3014866
  22. Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy.
    Acta Neuropathol. 1990;80(3):239-50 PMID: 2205076
  23. Theoretical expectations for deletional mutations in Duchenne muscular dystrophy.
    Am J Med Genet. 1988 Feb;29(2):445-51 PMID: 3354618
  24. Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.
    J Med Genet. 1990 May;27(5):292-7 PMID: 2191136
  25. A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male.
    Nature. 1987 Oct 8-14;329(6139):556-8 PMID: 2889145
  26. Sex ratio of the mutation frequencies in haemophilia A: estimation and meta-analysis.
    Hum Genet. 1990 Dec;86(2):139-46 PMID: 2148300
  27. DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure.
    J Med Genet. 1986 Dec;23(6):573-80 PMID: 2879929
  28. Segregation and sporadic cases of Duchenne muscular dystrophy in the Henan Province, China.
    Hum Hered. 1990;40(3):167-72 PMID: 2365377
  29. Theoretical considerations on germline mosaicism in Duchenne muscular dystrophy.
    J Med Genet. 1990 Nov;27(11):683-7 PMID: 2277383
  30. Mutants in Duchenne muscular dystrophy. Implications for prevention.
    Arch Neurol. 1988 Jan;45(1):84-5 PMID: 3337680
  31. Somatic mosaicism at the Duchenne locus.
    Am J Med Genet. 1990 Oct;37(2):187-90 PMID: 1978985
  32. Misdiagnosed normal fetus owing to undetected germinal mosaicism for DMD deletion.
    J Med Genet. 1989 Dec;26(12):790-1 PMID: 2575670
  33. Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations.
    Am J Hum Genet. 1988 Nov;43(5):620-9 PMID: 2903663
  34. Estimate of germinal mosaicism in Duchenne muscular dystrophy.
    J Med Genet. 1990 Nov;27(11):727-8 PMID: 2277394
  35. The genetic status of mothers of isolated cases of Duchenne muscular dystrophy.
    J Med Genet. 1983 Feb;20(1):1-11 PMID: 6842530
  36. Duchenne muscular dystrophy: the gene and the protein.
    Mol Biol Med. 1989 Feb;6(1):7-17 PMID: 2666821
  37. Direct diagnosis of carriers of Duchenne and Becker muscular dystrophy by amplification of lymphocyte RNA.
    Lancet. 1990 Dec 22-29;336(8730):1523-6 PMID: 1979364
  38. Mutation of the Duchenne muscular dystrophy gene associated with meiotic recombination.
    Clin Genet. 1986 Oct;30(4):347-9 PMID: 3791685
  39. Does unequal crossing over contribute to the mutation rate in Duchenne muscular dystrophy?
    Am J Med Genet. 1982 Aug;12(4):437-41 PMID: 7124796
  40. The population genetics of Duchenne: natural and artificial selection in Duchenne muscular dystrophy.
    J Med Genet. 1986 Dec;23(6):521-30 PMID: 3806638
  41. Gonadal mosaicism and genetic counseling for X-linked recessive lethals.
    Am J Hum Genet. 1974 Mar;26(2):207-22 PMID: 4823029
  42. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy.
    N Engl J Med. 1988 May 26;318(21):1363-8 PMID: 3285207
  43. Clinical studies in benign (Becker type) X-linked muscular dystrophy.
    Clin Genet. 1976 Oct;10(4):189-201 PMID: 975594
  44. Germinal mosaicism from grand-paternal origin in a family with Duchenne muscular dystrophy.
    Hum Genet. 1990 Dec;86(2):241-3 PMID: 1979959
  45. Germline mosaicism and Duchenne muscular dystrophy mutations.
    Nature. 1987 Oct 8-14;329(6139):554-6 PMID: 2889144
  46. Frequency of new mutants among boys with Duchenne muscular dystrophy.
    Am J Med Genet. 1980;7(1):27-34 PMID: 7211951
  47. Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs.
    Lancet. 1985 Mar 23;1(8430):655-8 PMID: 2858615
  48. Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy.
    Hum Genet. 1987 Mar;75(3):221-7 PMID: 2881877
  49. Germinal mosaicism in Duchenne muscular dystrophy.
    Hum Genet. 1988 Mar;78(3):282-4 PMID: 3346017
  50. Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene: isolation and use of J66 (DXS268), a distal intragenic marker.
    Genomics. 1987 Dec;1(4):329-36 PMID: 2896627
  51. Familial inheritance of a DXS164 deletion mutation from a heterozygous female.
    Am J Hum Genet. 1987 Aug;41(2):138-44 PMID: 2887110
Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
0340-6717
DOI
10.1007/BF00197255
Published
1992-01-00
Pages
249-57
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00197255 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2