Rhabdomyolysis and metabolic muscle disorders

Gene: ATP2A2

Green List (high evidence)

PMID: 39970126 reports a rare heterozygous missense ATP2A2 (alias symbol: SERCA2) variant (12:110777348G>A, c.1583G>A, p.R528Q) in 14 affected individuals from three unrelated families with recurrent rhabdomyolysis (an unaffected 6 year old child also carried the variant, however, symptoms of rhabdomyolysis may develop as he gets older). Haplotype analysis confirmed that the families were not related. In vitro and in vivo studies suggest that the variant affects ATP2A2 normal function, resulting in abnormal intracellular Ca2+ homeostasis in skeletal muscle, resulting in rhabdomyolysis.
Morphant zebrafish embryos (atp2a2a knockdown) had morphological and functional muscle abnormalities, including a reduced body length and trunk muscle area and a reduced locomotor activity in zebrafish larvae. This phenotype was rescued by wild-type human ATP2A2 mRNA but not variant ATP2A2 mRNA.
Sources: Literature

Created: 25 Feb 2025, 2:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Dominant rhabdomyolysis

Publications

• 39970126