Murtazina Aysylu, Demina Nina, Chausova Polina, Shchagina Olga, Borovikov Artem, Dadali Elena
Research Centre for Medical Genetics, 115478 Moscow, Russia.
Genes (Basel). 2022 Feb 13;13(2):341. doi: 10.3390/genes13020341.
Congenital myopathy associated with pathogenic variants in the 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 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 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.
与该基因致病性变异相关的先天性肌病长期以来一直被认为是美洲原住民肌病（NAM）。2017年，首例非美洲印第安人患有这种肌病的病例被报道。在此，我们报告首例俄罗斯籍NAM患者。该患者是一名17岁女性，该基因存在复合杂合单核苷酸变异：c.862A>T，p.（Lys288Ter）和c.93del，p.（Lys32ArgfsTer78）。她的表型比先前描述的患者更轻。据我们所知，这是首例同时具有无义变异和移码变异的患者。推测带有提前终止密码子的移码变异会导致无义介导的RNA降解。然而，该基因还有另外两种编码异构体，不受此移码变异影响。我们可以推测这些异构体可能部分执行该功能，并可能解释我们患者较轻的表型。
