The First Russian Patient with Native American Myopathy

Area of Science:

• Genetics and Molecular Biology
• Neuromuscular Disorders

Background:

• Congenital myopathy linked to pathogenic STAC3 gene variants was historically identified as Native American myopathy (NAM).
• Previous research documented the first non-Amerindian patient with this condition in 2017, expanding the known demographic affected by NAM.

Observation:

• This report details the first Russian patient diagnosed with Native American myopathy.
• The patient, a 17-year-old female, exhibits compound-heterozygous variants in the STAC3 gene: c.862A>T (p.Lys288Ter) and c.93del (p.Lys32ArgfsTer78).

Findings:

• The patient presents a milder clinical phenotype compared to previously described individuals with STAC3-related myopathy.
• This case represents the first documented instance of a patient with both nonsense and frameshift variants in the STAC3 gene.

Implications:

• The frameshift variant is predicted to trigger nonsense-mediated RNA decay, potentially impacting STAC3 protein function.
• The existence of two additional coding isoforms of STAC3, unaffected by the frameshift variant, may offer partial functional compensation, possibly explaining the observed milder phenotype.