DOI: 10.24075/brsmu.2019.034


Clinical and molecular-genetic profiles of patients with morphological indications of congenital multicore myopathy

Kozina AA1,5, Shatalov PA3,5, Baranich TI1, Artemieva SB3, Kupriyanova AG3, Baryshnikova NV1,5, Krasnenko AYu1,5, Ilinsky VV1,2,5, Sukhorukov VS1,4
About authors

1 Pirogov Russian National Research Medical University, Moscow, Russia

2 Institute of Biomedical Chemistry, Moscow, Russia

3 Veltischev Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia

4 Research Center of Neurology, Moscow, Russia

5 Genotek Ltd., Moscow, Russia

Correspondence should be addressed: Anastasia A. Kozina
Nastavnichesky per 17, bld. 1, Moscow, 105120; ur.ketoneg@rotcod

About paper

Author contribution: Kozina AA — literature analysis, analysis and interpretation of exome sequencing data, manuscript preparation; Shatalov PA — data acquisition, microscopy, manuscript preparation; Baranich TI — microscopy; Artemieva SB — medical histories and neurological examinations; Kupriyanova AG — clinical data acquisition; Baryshnikova NV — literature analysis, analysis and interpretation of exome sequencing data, manuscript preparation; Krasnenko AYu — exome sequencing; Ilinsky VV — exome sequencing; Sukhorukov VS — study design, data acquisition.

Received: 2019-02-07 Accepted: 2019-04-19 Published online: 2019-04-30

Congenital core myopathies are a clinically and genetically heterogenous group of congenital myopathies that share a specific histopathological feature: areas of reduced oxidative activity in muscle fibers. The relationship between clinical, genetic and morphological characteristics of this group of disorders remains understudied. The aim of this work was to compare clinical presentations and morphological phenotypes of patients with congenital myopathies/myodystrophy to the data yielded by massively parallel exome sequencing. Eight children were included in the study: 2 boys and 6 girls aged 3 to 14 years. Their biopsy material was analyzed by light and electron microscopy. Sequencing was performed on HiSeq2500. Mutations were detected in 7 (87.5%) of 8 participants. Six children had 8 mutations in the genes associated with congenital core myopathies; one patient had 2 mutations in the LAMA2 gene implicated in merosin-deficient muscular dystrophy. The proportions of patients with mutations in RYR1 and SEPN1 were equal (42.86%). Of 10 detected mutations, 3 had not been previously described, including c.7561G>A in RYR1, c.485C>A in SEPN1 and p.Cys1136Arg in LAMA2. The clinical and morphological features of core myopathies suggest that genetic causes of this group of disorders should not be limited to RYR1 and SEPN1 genes only. This necessitates the search for and the study of other genes implicated in congenital myopathies or myodystrophy using state-of-the-art molecular genetic tools.

Keywords: muscle biopsy, congenital central core disease, congenital multicore myopathies, RYR1 gene, SEPN1 gene, LAMA2 gene, exome sequencing