Pure distal myopathy involving the TDP-43 protein

A team of researchers and clinicians from Lyon report two unrelated families from the Ain region with late-onset distal myopathy with no signs likely to suggest associated motor neurone damage:

• A total of eight adult patients were studied, the disease being transmitted in an autosomal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. fashion, with variable penetrance,
• The same missense variant of the TARDBP gene was identified in all patients,
• Functional studies carried out in collaboration with a German laboratory have confirmed its pathogenic nature and its involvement in the accumulation of the TDP-43 protein inside cells.

This is the first time that this gene has been implicated in a pure form of adult distal myopathy, without associated ALS and/or fronto-temporal dementia.

The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis. Zibold J, Lessard LER, Picard F et al. Brain. 2023 Dec.