Somatic mosaicism due to a reversion variant causing hemi-atrophy

A novel variant of dystrophinopathy

Jaya Punetha, Simin Mansoor, Tulio Bertorini, Akanchha Kesari, Kristy J. Brown, Eric P. Hoffman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We describe a case of hemi-atrophy in a young adult male, with a positive family history of three maternal uncles with Duchenne muscular dystrophy (DMD). The patient showed progressive weakness localized to the left side, an abnormal electromyography, and creatine kinase levels >3000 IU/l. Muscle biopsy showed both dystrophin-positive and -negative myofibers. An out-of-frame duplication variant in DMD, that is, c.(93+1-94-1)-(649+1-650-1)dup(p.?) resulting in duplication of exons 3-7 was inherited, but the muscle biopsy showed dystrophin mRNA with and without the duplication. Dystrophin quantification using mass spectrometry showed 25% normal dystrophin protein levels in the muscle biopsy from the stronger right side. Sex chromosome aneuploidy was ruled out. We conclude that the patient inherited the duplication variant, but early in development an inner cell mass underwent a somatic recombination event removing the duplication and restoring dystrophin expression. To our knowledge, this is the first report of a reversion leading to somatic mosaicism in DMD.

Original languageEnglish (US)
Pages (from-to)1511-1514
Number of pages4
JournalEuropean Journal of Human Genetics
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Dystrophin
Mosaicism
Atrophy
Duchenne Muscular Dystrophy
Biopsy
Muscles
Sex Chromosomes
Electromyography
Aneuploidy
Creatine Kinase
Genetic Recombination
Young Adult
Exons
Mass Spectrometry
Mothers
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Somatic mosaicism due to a reversion variant causing hemi-atrophy : A novel variant of dystrophinopathy. / Punetha, Jaya; Mansoor, Simin; Bertorini, Tulio; Kesari, Akanchha; Brown, Kristy J.; Hoffman, Eric P.

In: European Journal of Human Genetics, Vol. 24, No. 10, 01.10.2016, p. 1511-1514.

Research output: Contribution to journalArticle

Punetha, Jaya ; Mansoor, Simin ; Bertorini, Tulio ; Kesari, Akanchha ; Brown, Kristy J. ; Hoffman, Eric P. / Somatic mosaicism due to a reversion variant causing hemi-atrophy : A novel variant of dystrophinopathy. In: European Journal of Human Genetics. 2016 ; Vol. 24, No. 10. pp. 1511-1514.
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