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 dominant 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 mutation that had gone unnoticed.
This work confirms the existence of this very exceptional case, which can be confusing when interpreting genetic tests.
