Miyoshi myopathy associated with spine rigidity and multiple contractures: a case report.

BACKGROUND: Dysferlinopathy is a phenotypically heterogeneous group of hereditary diseases caused by mutations in the DYSF gene. Early contractures are considered rare, and rigid spine syndrome in dysferlinopathy has been previously reported only once. CASE PRESENTATION: We describe a 23-year-old patient with Miyoshi myopathy with a rigid spine and multiple contractures, a rare phenotypic variant. The disease first manifested when the patient was 13 years old, with fatigue of the gastrocnemius muscles and the development of pronounced contractures of the Achilles tendons, flexors of the fingers, and extensors of the toes, followed by the involvement of large joints and the spine. Magnetic resonance imaging revealed signs of connective tissue and fatty replacement of the posterior muscles of the thighs and lower legs. Edema was noted in the anterior and medial muscle groups of the thighs, lower legs, and the multifidus muscle of the back. Whole genome sequencing revealed previously described mutations in the DYSF gene in exon 39 (c.4282 C > T) and intron 51 (c.5785-824 C > T). An immunohistochemical analysis and Western blot showed the complete absence of dysferlin protein expression in the muscle fibers. CONCLUSIONS: This case expands the range of clinical and phenotypic correlations of dysferlinopathy and complements the diagnostic search for spine rigidity.

Genetic screening of an endemic mutation in the DYSF gene in an isolated, mountainous population in the Republic of Dagestan.

BACKGROUND: Dysferlinopathy has a high prevalence in relatively isolated ethnic groups where consanguineous marriages are characteristic and/or the founder effect exists. However, the frequency of endemic mutations in most isolates has not been investigated. METHODS: The prevalence of the pathological DYSF gene variant (NM_003494.4); c.200_201delinsAT, p. Val67Asp (rs121908957) was investigated in an isolated Avar population in the Republic of Dagestan. Genetic screenings were conducted in a remote mountainous region characterized by a high level of consanguinity among its inhabitants. In total, 746 individuals were included in the screenings. RESULTS: This pathological DYSF gene variant causes two primary phenotypes of dysferlinopathy: limb-girdle muscular dystrophy (LGMD) type R2 and Miyoshi muscular dystrophy type 1. Results indicated a high prevalence of the allele at 14% (95% confidence interval [CI]: 12-17; 138 out of 1518 alleles), while the allele in the homozygous state was detected in 29 cases-3.8% (CI: 2.6-5.4). The population load for dysferlinopathy was 832.3 ± 153.9 per 100,000 with an average prevalence of limb-girdle muscular dystrophies ranging from 0.38 ± 0.38 to 5.93 ± 1.44 per 100,000. CONCLUSION: A significant burden of the allele was due to inbreeding, as evidenced by a deficiency of heterozygotes and the Wright fixation index equal to 0.14 (CI 0.06-0.23).

COVID-19 pandemic in Saint Petersburg, Russia: Combining population-based serological study and surveillance data.

BACKGROUND: The COVID-19 pandemic in Russia has already resulted in 500,000 excess deaths, with more than 5.6 million cases registered officially by July 2021. Surveillance based on case reporting has become the core pandemic monitoring method in the country and globally. However, population-based seroprevalence studies may provide an unbiased estimate of the actual disease spread and, in combination with multiple surveillance tools, help to define the pandemic course. This study summarises results from four consecutive serological surveys conducted between May 2020 and April 2021 at St. Petersburg, Russia and combines them with other SARS-CoV-2 surveillance data. METHODS: We conducted four serological surveys of two random samples (May-June, July-August, October-December 2020, and February-April 2021) from adults residing in St. Petersburg recruited with the random digit dialing (RDD), accompanied by a telephone interview to collect information on both individuals who accepted and declined the invitation for testing and account for non-response. We have used enzyme-linked immunosorbent assay CoronaPass total antibodies test (Genetico, Moscow, Russia) to report seroprevalence. We corrected the estimates for non-response using the bivariate probit model and also accounted the test performance characteristics, obtained from independent assay evaluation. In addition, we have summarised the official registered cases statistics, the number of hospitalised patients, the number of COVID-19 deaths, excess deaths, tests performed, data from the ongoing SARS-CoV-2 variants of concern (VOC) surveillance, the vaccination uptake, and St. Petersburg search and mobility trends. The infection fatality ratios (IFR) have been calculated using the Bayesian evidence synthesis model. FINDINGS: After calling 113,017 random mobile phones we have reached 14,118 individuals who responded to computer-assisted telephone interviewing (CATI) and 2,413 provided blood samples at least once through the seroprevalence study. The adjusted seroprevalence in May-June, 2020 was 9.7% (95%: 7.7-11.7), 13.3% (95% 9.9-16.6) in July-August, 2020, 22.9% (95%: 20.3-25.5) in October-December, 2021 and 43.9% (95%: 39.7-48.0) in February-April, 2021. History of any symptoms, history of COVID-19 tests, and non-smoking status were significant predictors for higher seroprevalence. Most individuals remained seropositive with a maximum 10 months follow-up. 92.7% (95% CI 87.9-95.7) of participants who have reported at least one vaccine dose were seropositive. Hospitalisation and COVID-19 death statistics and search terms trends reflected the pandemic course better than the official case count, especially during the spring 2020. SARS-CoV-2 circulation showed rather low genetic SARS-CoV-2 lineages diversity that increased in the spring 2021. Local VOC (AT.1) was spreading till April 2021, but B.1.617.2 substituted all other lineages by June 2021. The IFR based on the excess deaths was equal to 1.04 (95% CI 0.80-1.31) for the adult population and 0.86% (95% CI 0.66-1.08) for the entire population. CONCLUSION: Approximately one year after the COVID-19 pandemic about 45% of St. Petersburg, Russia residents contracted the SARS-CoV-2 infection. Combined with vaccination uptake of about 10% it was enough to slow the pandemic at the present level of all mitigation measures until the Delta VOC started to spread. Combination of several surveillance tools provides a comprehensive pandemic picture.