The First Russian Patient with Native American Myopathy

Abstract

Congenital myopathy associated with pathogenic variants in the STAC3 gene has long been considered native American myopathy (NAM). In 2017, the first case of a non-Amerindian patient with this myopathy was described. Here, we report the first Russian patient with NAM. The patient is a 17-year-old female with compound-heterozygous single nucleotide variants in the STAC3 gene: c.862A>T, p.(Lys288Ter) and c.93del, p.(Lys32ArgfsTer78). She has a milder phenotype than the earlier described patients. To our knowledge, this is the first case of a patient who had both nonsense and frameshift variants. It is assumed that the frameshift variant with premature stop codon lead to nonsense-mediated RNA decay. However, there are two additional coding isoforms of the STAC3 gene, which are not affected by this frameshift variant. We can speculate that these isoforms may partially carry out the function, and possibly explain the milder phenotype of our patient.

Why Craniofacial Surgeons/Researchers Need to be Aware of Native American Myopathy?

“…However, a milder form of the disease has recently been described in non-Native American patients. 3,4,7,8 Patients' serum creatine kinase is typically in the normal range, and electromyography shows myopathic changes. A unique feature of this disease, as first described by Bailey and Bloch and shared only with two other muscle diseases, is patients' susceptibility to MH (5,6).…”

“…With more cases reported worldwide, the phenotypic spectrum CMYO13 is expanding to include milder, less affected cases with minimal muscle weakness. [3] Similar to congenital myopathies, CMYO13 patients typically present with proximal arm/leg and axial weakness. The progression of weakness is variable in the literature, as some patients' weaknesses are observed to be static while others are progressive [3,5,7].…”

“…[3] Similar to congenital myopathies, CMYO13 patients typically present with proximal arm/leg and axial weakness. The progression of weakness is variable in the literature, as some patients' weaknesses are observed to be static while others are progressive [3,5,7]. Such rapid progression of muscle weakness in some CMYO13 cases is rarely observed in congenital myopathies.…”

Editorial for the Genetics of Muscular Dystrophies from the Pathogenesis to Gene Therapy Special Issue

“…On the other hand, Soontrapa and Liewluck [ 9 ] reported the spectrum of mono- and bi-allelic variants in anoctamin 5 (ANO5), including LGMDR12, Miyoshi distal myopathy type 3, pseudometabolic phenotype, and asymptomatic hyperCKemia. Murtazina and co-workers [ 10 ] described the first Russian patient with Native American congenital myopathy (NAM) due to pathogenic variants in the STAC3 gene and hypothesized the possible contribution of muscle-specific isoforms on the clinical phenotype.…”

“…They also highlight that it is not only important for a complete and precise diagnosis [ 3 , 5 ] to propose timely personalized and pathogenic therapies [ 4 , 8 ], but also to consider potential genetic modifiers [ 6 , 7 ]. We anticipate that this Special Issue will help researchers dismiss concepts that are no longer applicable, such as the presence of homogeneous phenotypes [ 1 , 9 , 10 ] and the concepts of “one gene = one phenotype” to overcome the “single-dimension” paradigm traditionally used to describe genotype–phenotype relationships [ 2 ]…”