The involvement of the MLIP gene in the occurrence of acute episodes of rhabdomyolysis associated with exertional myalgia from early childhood was first published in October 2021. This gene encodes the Muscular LMNA-interacting protein (MLIP), which interacts with lamins A/C and is thought to play a role in the regulation of transcriptional activators during cardiac stress.
A Quebec team reports the observation of a man who presented at the age of 50 years with a distal myopathy predominantly on the foot lifts:
- around the age of 5, he had consulted because he could not skate or run as fast as his friends, without having a clear diagnosis;
- around the age of 60, he developed a hyperlordosis and a Trendelenburg gait, with cramps, myalgias, increase of CPK but without rhabdomyolysis;
- in the lack of results with different gene panels, RNA sequencing revealed a homozygous nonsense mutation in exon 5 of the MLIP gene, confirmed by the Sanger method;
- RT-PCR and long-read sequencing showed a significant change in transcription in the patient: fewer transcripts containing the exon 5 mutation but new transcripts containing exon 4 and an overproduction of lamin A.
The authors conclude not only that there are adult cases of MLIP-related myopathy, but also that long-read sequencing is useful for studying variants of unknown significance (VUS).
