A new series of cases of autosomal dominant calpainopathy

French and Danish researchers have published data on patients suffering from primary calpainopathy and deviating from the usual pattern of inheritance:

• the 4 new cases are in addition to the exceedingly rare cases in which 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. inheritance (LGMD-D4 according to the revised nomenclature for LGMD) has been clearly established,
• they involved a father and his son, and two sporadic cases,
• in each case, a single pathogenic variant of the CAPN3 gene was present and accompanied by mild clinical signs and symptoms,
• the Western-Blot demonstrated a significant absence of calpain-3; A very advanced NGS analysis (up to the entire genome) ruled out the hypothesis of a second mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). that had gone unnoticed.

This work confirms the existence of this very exceptional case, which can be confusing when interpreting genetic tests.

Variants in CAPN3 Causing Autosomal Dominant Limb-Girdle Muscular Dystrophy Combined With Calpain-3 Deficiency. Krag T, Nasho E, Brady L, et al. Hum Mutat. 2025 Mar