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Equal proportions of affected cells in muscle and blood of a mosaic carrier of facioscapulohumeral muscular dystrophy

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Abstract

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of D4Z4 repeat on 4q35. It displays a remarkable inter- and intra-familial clinical variability ranging from severe phenotype to asymptomatic carriers. Mosaicism for the contracted FSHD-sized allele is a recurrent finding, but only DNA from lymphocytes had been studied. It is currently not known if mosaicism is unequally distributed between different tissues and if muscle is relatively spared for the presence of the disease allele in mosaic asymptomatic carriers of a disease allele. Here we compare DNA extracted from peripheral blood lymphocytes (PBL), fibroblasts and muscle from a mosaic asymptomatic female carrier and mother of a FSHD patient. PFGE analysis showed a complex allelic segregation: two independent mitotic rearrangement episodes occurred, resulting in mosaicism for a contracted D4Z4 repeat on 4q35 in the mother and mosaicism for an expanded D4Z4 repeat on 10q26 in the affected daughter. The results show that the proportion of mosaicism in PBL and muscle were comparable, while in fibroblasts there was some variation in the mosaicism, which might be caused by culturing artefacts. This finding supports the hypothesis that a mitotic contraction of D4Z4 is an early embryonic event and indicates that the degree of mosaicism in PBL is representative for that of muscle.

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Acknowledgments

The members of this family, who were essential for this work and Constancia Urbani are gratefully acknowledged. A gratitude is also expressed to Dr. Mariz Vainzof, Telma Gouveia and Corrie van Teijlingen for helping with culturing and Dr. Ivo Pavanello for the muscle biopsies. This work was supported by grants from FAPESP-CEPID and CNPq. SMvdM is supported by grants from the Netherlands Organisation for Scientific Research (NWO) (917.56.338), the Prinses Beatrix Fonds, the Stichting Spieren voor Spieren, the Muscular Dystrophy Association USA, the National Institutes of Health, and the Shaw family.

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Author notes

  1. Maria Manuela O. Tonini

    Present address: Inserm U 741—Institut Jacques Monod, Tour 43/2eme etage/couloir 43-44, 2 Place Jussieu, 75251, Paris, Cedex 05, France

Authors and Affiliations

  1. Departamento de Biologia, Human Genome Research Center, Universidade de São Paulo, Rua do Matão, 277 Cidade Universitária, CEP: 05508-090, São Paulo, SP, Brazil

    Maria Manuela O. Tonini, Rita C.M. Pavanello, Antonia M.P. Cerqueira & Mayana Zatz

  2. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Richard J.L.F. Lemmers, Rune R. Frants & Silvere M. van der Maarel

Authors
  1. Maria Manuela O. Tonini
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  2. Richard J.L.F. Lemmers
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  3. Rita C.M. Pavanello
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  4. Antonia M.P. Cerqueira
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  5. Rune R. Frants
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  6. Silvere M. van der Maarel
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  7. Mayana Zatz
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Correspondence to Mayana Zatz.

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Tonini, M.M.O., Lemmers, R.J., Pavanello, R.C. et al. Equal proportions of affected cells in muscle and blood of a mosaic carrier of facioscapulohumeral muscular dystrophy. Hum Genet 119, 23–28 (2006). https://doi.org/10.1007/s00439-005-0100-2

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  • DOI: https://doi.org/10.1007/s00439-005-0100-2

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