OBJECTIVE: To report a case of congenital myopathy caused by RYR1 gene complex heterozygous mutation and analyze the pathogenicity of the mutation. Method The clinical manifestation, laboratory examination, imaging findings, muscle pathology and gene test results of a child with congenital myopathy were analyzed retrospectively. Combined with literature review, it is analyzed and discussed. Result The child, female, was admitted to hospital because of \"dyspnea for 22 min after asphyxia resuscitation\". The main manifestations are low muscle tension, the original reflex cannot be drawn out, the trunk and proximal muscles are weak, and the tendon reflex is not drawn out. The pathological signs were negative. The electrolyte of blood liver and kidney function, blood thyroid and blood ammonia were not abnormal, and creatine kinase increased temporarily. Electromyography suggests myogenic damage. Whole exome sequencing showed that there was a new compound heterozygous variation in RYR1 gene c.14427_ 14429del/c.14138C＞T.Western blot showed that the expression of RYR1 protein in patients was significantly lower than that in normal controls. Conclusion The compound heterozygous variation of RYR1 gene c.14427 was reported for the first time in China_ 14429del/c.14138c > t is the pathogenic gene of the child. The new discovery of RYR1 gene spectrum was revealed, which expanded the RYR1 gene spectrum.

[This corrects the article DOI: 10.3389/fneur.2021.761636.].

Congenital myopathies are a group of rare neuromuscular diseases characterized by specific histopathological features. The relationship between the pathologies and the genetic causes is complex, and the prevalence of myopathy-causing genes varies among patients from different ethnic groups. The aim of the present study was to characterize congenital myopathies with infancy onset among patients registered at our institution.
This retrospective study enrolled 56 patients based on the pathological and/or genetic diagnosis. Clinical, histopathological and genetic features of the patients were analysed with long-term follow-up.
Twenty-six out of 43 patients who received next-generation sequencing had genetic confirmation, and RYR1 variations (12/26) were the most prevalent. Eighteen novel variations were identified in 6 disease-causing genes, including RYR1, NEB, TTN, TNNT1, DNM2 and ACTA1. Nemaline myopathy (17/55) was the most common histopathology. The onset ages ranged from birth to 1 year. Thirty-one patients were followed for 3.83 ± 3.05 years (ranging from 3 months to 11 years). No patient died before 1 year. Two patients died at 5 years and 8 years respectively. The motor abilities were stable or improved in 23 patients and deteriorated in 6 patients. Ten (10/31) patients developed respiratory involvement, and 9 patients (9/31) had mildly abnormal electrocardiograms and/or echocardiograms.
The severity of congenital myopathies in the neonatal/infantile period may vary in patients from different ethnic groups. More concern should be given to cardiac monitoring in patients with congenital myopathies even in those with static courses.

Background: Congenital myopathy constitutes a heterogeneous group of orphan diseases that are mainly classified on the basis of muscle biopsy findings. This study aims to estimate the prevalence of congenital myopathy through a systematic review and meta-analysis of the literature. Methods: The PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched for original research articles published in English prior to July 30, 2021. The quality of the included studies was assessed by a checklist adapted from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random effects model. Heterogeneity was assessed using the Cochrane Q statistic as well as the I 2 statistic. Results: A total of 11 studies were included in the systematic review and meta-analysis. Of the 11 studies included, 10 (90.9%) were considered medium-quality, one (9.1%) was considered low-quality, and no study was assessed as having a high overall quality. The pooled prevalence of congenital myopathy in the all-age population was 1.50 (95% CI, 0.93-2.06) per 100,000, while the prevalence in the child population was 2.73 (95% CI, 1.34-4.12) per 100,000. In the pediatric population, the prevalence among males was 2.92 (95% CI, -1.70 to 7.55) per 100,000, while the prevalence among females was 2.47 (95% CI, -1.67 to 6.61) per 100,000. The prevalence estimates of the all-age population per 100,000 were 0.20 (95% CI 0.10-0.35) for nemaline myopathy, 0.37 (95% CI 0.21-0.53) for core myopathy, 0.08 (95% CI -0.01 to 0.18) for centronuclear myopathy, 0.23 (95% CI 0.04-0.42) for congenital fiber-type disproportion myopathy, and 0.34 (95% CI, 0.24-0.44) for unspecified congenital myopathies. In addition, the prevalence estimates of the pediatric population per 100,000 were 0.22 (95% CI 0.03-0.40) for nemaline myopathy, 0.46 (95% CI 0.03-0.90) for core myopathy, 0.44 (95% CI 0.03-0.84) for centronuclear myopathy, 0.25 (95% CI -0.05 to 0.54) for congenital fiber-type disproportion myopathy, and 2.63 (95% CI 1.64-3.62) for unspecified congenital myopathies. Conclusions: Accurate estimates of the prevalence of congenital myopathy are fundamental to supporting public health decision-making. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher-quality studies on orphan diseases.

BACKGROUND: Congenital fiber-type disproportion (CFTD) is a form of congenital myopathy. CFTD is rare, especially when presenting in patients with critical illnesses. Here, we report a case of CFTD presenting with type II respiratory failure after delivery and provide a review of the literature on CFTD.
METHODS: A 30-year-old woman was admitted to the obstetrics department of our hospital with premature rupture of the fetal membrane and with 7 h of regular contractions. After delivery, the patient experienced a refractory type II respiratory failure. Physical examination along with diagnostic procedures such as electromyography and biopsy confirmed CFTD. Use of invasive ventilator followed by intermittent use of noninvasive ventilator attenuated her symptoms. The patient recovered after ventilator-assisted respiration and was weaned off the noninvasive ventilator on the seventh day postpartum.
CONCLUSIONS: Congenital myopathy should be considered a differential diagnosis for type II respiratory failures that cannot be attributed to other diseases.

High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort.
We analyzed clinical and genetic data in a cohort of patients with biallelic pathogenic or likely pathogenic TTN variants. The cohort included both previously reported cases (100 patients from 81 unrelated families) and unreported cases (23 patients from 20 unrelated families).
Overall, 132 causative variants were identified in cohort members. More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene. The remaining patients had a distal or proximal phenotype and a childhood or later (noncongenital) onset. All noncongenital cases had at least one pathogenic variant in one of the final three TTN exons (362-364).
Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.

Ryanodine receptor 1 (RYR1), myosin heavy chain 7 (MYH7), and selenoprotein N1 (SEPN1) mutations are associated with core myopathies. RYR1 mutations cause most cases of central core disease (CCD).
We screened 8 Chinese patients with clinicopathological diagnosis of CCD. Genetic analysis was carried out by targeted next generation sequencing (NGS) to identify causative genes. Variants were assessed for pathogenicity using bioinformatic approaches, and NGS results were confirmed by Sanger sequencing.
One novel (p.L4578V) and heterozygous missense mutations in RYR1 were identified in 7 patients. Two patients carried a novel mutation, 1 had p.M4640R, 3 had p.R4861H, and 1 had p.R4861C. All patients had mild to moderate severity phenotypes. Histopathological findings demonstrated central cores and type I fiber predominance.
NGS is an efficient strategy to identify variants in RYR1 in CCD. However, genetic results revealed by NGS must be combined with clinicopathologic features to validate the diagnosis. Muscle Nerve, 2016 Muscle Nerve 54: 432-438, 2016.

Muscular dystrophies and congenital myopathies are a large group of heterogeneous inherited muscle disorders. The spectrum of muscular dystrophies and congenital myopathies extends to more than 50 diseases today, even excluding the common forms Duchenne Muscular Dystrophy, Myotonic Dystrophy and Facioscapulohumeral Dystrophy. Unfortunately, even by critical clinical evaluation and muscle pathology, diagnosis is still difficult. To potentially remediate this difficulty, we applied a microarray-based targeted next-generation sequencing (NGS) technology to diagnose these patients. There were 55 consecutive unrelated patients who underwent the test, 36 of which (65%) were found to have a causative mutation. Our result shows the accuracy and efficiency of next-generation sequencing in clinical circumstances and reflects the features and relative distribution of inherited myopathies in the Chinese population.