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Somatic mosaicism for a deletion of the dystrophin gene in a carrier of Becker muscular dystrophy

  • Medical Genetics
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Abstract

Duchenne muscular dystrophy (DMD) and the allelic milder form of Becker muscular dystrophy (BMD) are caused by mutations of the dystrophin gene on the short arm of the X chromosome. One third of affected indviduals are expected to result from de novo mutations. Genetic counselling of families with sporadic cases is complicated by the potential meiotic origin of the mutation in the mother resulting in germline mosaicism. Here we present direct evidence for combined somatic and germline mosaicism for a deletion of the dystrophin gene, thereby proving the mitotic origin of this deletion and pinpointing a further potential pitfall for genetic counselling. The mother of a BMD son and a BMD carrier daughter, both carrying a deletion of dystrophin cDNA 7 (0.5 kb Hind III fragment) and cNDA 8, was herself clinically healthy and had normal creatine kinase levels. A muscle specimen of the mother showed mild overall pathology as well as focal dystrophin deficiency. In contrast chromosomal in situ suppression (CISS) hybridization of metaphase chromosomes using a cosmid clone of the corresponding cDNA deleted in her son revealed no evidence of somatic mosaicism in their lymphocytes. These results emphasize the value of an approach correlating genetic and immunological data for the definition of a carrier state in BMD or DMD. The possibility of somatic mosaicism should be considered when genetic counselling of a family with a sporadic case of BMD or DMD is performed.

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Abbreviations

BMD:

Becker muscular dystrophy

CK:

creatine kinase

CISS:

chromosomal in situ suppression

DMD:

Duchenne muscular dystrophy

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Authors and Affiliations

  1. Department of Paediatrics, University of Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf, Federal Republic of Germany

    T. Voit

  2. Department of Neuropathology, University of Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf, Federal Republic of Germany

    E. Neuen-Jacob

  3. Institute of Human Genetics and Anthropology, University of Heidelberg, Im Neuenheimer Feld 328, W-6900, Heidelberg, Federal Republic of Germany

    V. Mahler, A. Jauch & M. Cremer

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  2. E. Neuen-Jacob
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  4. A. Jauch
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  5. M. Cremer
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Voit, T., Neuen-Jacob, E., Mahler, V. et al. Somatic mosaicism for a deletion of the dystrophin gene in a carrier of Becker muscular dystrophy. Eur J Pediatr 151, 112–116 (1992). https://doi.org/10.1007/BF01958954

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  • DOI: https://doi.org/10.1007/BF01958954

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