Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied.

Leigh syndrome (LS), also known as infantile subacute necrotizing encephalopathy, is the most frequent mitochondrial disorder in children. Recently, more than 80 genes have been associated with LS, which greatly complicates the diagnosis. In this article, we present clinical and molecular findings of 219 patients with LS and give the detailed description of three cases with rare findings in nuclear genes MORC2, NARS2 and VPS13D, demonstrating wide genetic heterogeneity of this mitochondrial disease. The most common cause of LS in Russian patients are pathogenic variants in the SURF1 gene (44.3% of patients). The most frequent pathogenic variant is c.845_846delCT (66.0% of mutant alleles; 128/192), which is also widespread in Eastern Europe. Five main LS genes, SURF1, SCO2, MT-ATP6, MT-ND5 and PDHA1, account for 70% of all LS cases in the Russian Federation. Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3, including two genes previously associated with Leigh-like phenotypes—MORC2 and VPS13D. We found 49 previously undescribed nucleotide variants, including two deep intronic variants which affect splicing.

Thomsen’s and Becker’s diseases are the most prevalent nondystrophic myotonias. Their frequency varies, according to different sources, from 1: 100000 to 1: 10000. Thomsen’s myotonia is autosomal dominant, and Becker’s myotonia is autosomal recessive. Both diseases result from mutations of the CLCN1 gene encoding chloride ion channels of skeletal muscles. Molecular genetic analysis of the CLCN1 gene has been performed in patients with diagnoses of nondystrophic Thomsen’s and Becker’s myotonias living in the Russian Federation. A sample of 79 unrelated probands with nondystrophic Thomsen’s and Becker’s myotonias and 44 their relatives has been formed in the Laboratory of DNA Diagnosis of the Medical Genetic Research Center of the Russian Academy of Medical Sciences. Forty CLCN1 gene mutations have been found in a total of 118 chromosomes of 66 probands, including 21 familial and 45 sporadic cases. About half the mutations detected (45%) have been found for the first time; they are not described in the SNP database (ncbi.nlm.nih.gov). The following mutations (substitutions) have been detected in more than one chromosome, accounting for a total of 59.3% of chromosomes with mutations: Gly190Ser (5.9%), c.1437_1450del14 (9.3%), Ala493Glu (5.1%), Thr550Met (3.4%), Tyr686Stop (5.1%), and Arg894Stop (30.5%).