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Limb -girdle type muscular dystrophy is a group of muscle myopathies with the progressive muscle change mainly in the pelvic girdle and shoulder girdle. It often occurs in childhood with obvious genetic heterogeneity. We reported a case of limb-girdle type muscular dystrophy that a child was diagnosed firstly as bronchopneumonia. The whole exome sequencing technology was used to screen the variant sites of related genes, Sanger sequencing technology was used to analyze and verify the suspected variant sites. The child was found to have the compound heterozygous mutations of DYSF gene (NM_003494), a c.2974T>C(p.W992R) mutation in exon 12 and a c.1169A>G (p.D390G) mutation in exon 28. The locus c.2974T>C (p.W992R) was inherited from the father, and the locus c.1169A>G (p.D390G) from the mother. Both variants were the truncating variants (PVS1). They were not included in the gene database of normal population, so they were rare variants (PM2_Supporting). Therefore, both variants were assessed as the likely pathogenic variants. The validation results of Sanger sequencing were consistent with the results of whole exome sequencing. Accordingly, the child was finally diagnosed as limb-girdle muscular dystrophy type 2B. Whole exome sequencing technology can provide genetic analysis and prenatal diagnosis for limb-girdle type muscular dystrophy, and has key value in clinical decision-making, genetic counseling and re-pregnancy planning. [ABSTRACT FROM AUTHOR]

Limb-girdle muscular dystrophy R9 (LGMDR9) is a progressive and disabling genetic muscle disease. Sleep is relevant in the patient care as it impacts on health, functioning, and well-being. LGMDR9 may potentially affect sleep by physical or emotional symptoms, myalgia, or sleep-disordered breathing (SDB) through cardiorespiratory involvement. The objective was to investigate the occurrence of insomnia and unrecognized or untreated SDB in LGMDR9, associated factors, and relationships with fatigue and health-related quality of life (HRQoL). All 90 adults in a Norwegian LGMDR9 cohort received questionnaires on sleep, fatigue, and HRQoL. Forty-nine of them underwent clinical assessments and 26 without mask-based therapy for respiration disorders additionally underwent polysomnography (PSG) and capnometry. Among 77 questionnaire respondents, 31% received mask-based therapy. The prevalence of insomnia was 32% of both those with and without such therapy but was significantly increased in fatigued respondents (54% vs 21%). Insomnia levels correlated inversely with mental HRQoL. Among 26 PSG candidates, an apnea–hypopnea index (AHI) ≥ 5/h was observed in 16/26 subjects (≥ 15/h in 8/26) with median 6.8 obstructive apneas and 0.2 central apneas per hour of sleep. The AHI was related to advancing age and an ejection fraction < 50%. Sleep-related hypoventilation was detected in one subject. Fatigue severity did not correlate with motor function or nocturnal metrics of respiration or sleep but with Maximal Inspiratory Pressure (r = − 0.46). The results indicate that insomnia and SDB are underrecognized comorbidities in LGMDR9 and associated with HRQoL impairment and heart failure, respectively. We propose an increased attention to insomnia and SDB in the interdisciplinary care of LGMDR9. Insomnia and pulmonary function should be examined in fatigued patients. [ABSTRACT FROM AUTHOR]

Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3–R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.

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Purpose Caveolinopathy is a disease caused by caveolin-3 (CAV3) mutations that shows a wide clinical spectrum, including isolated hyperCKemia and limb-girdle muscular dystrophy. While recent advances in next-generation sequencing (NGS) have enabled earlier diagnosis of this disease, it remains difficult to predict the clinical course of each patient. Methods This study summarizes the clinical presentations of 13 genetically confirmed caveolinopathy patients in four Korean families. Genetic diagnosis was performed using NGS technologies for probands and Sanger sequencing for the other family members. Results Four coding mutations were found (p.Val103_Val104del, p.Asp28Glu, p.Pro105Leu, and p.Arg27Gln), and each family showed autosomal dominant inheritance. While all 13 cases had hyperCKemia, only five of them showed some myopathic features including ankle contracture, calf hypertrophy, exercise intolerance, and muscle cramping. This high proportion of asymptomatic cases suggests both that these mutations may be associated with a mild phenotype and that caveolinopathy may be an underdiagnosed disease. Conclusion This study extends our understanding of caveolinopathy; in particular, the findings suggest the need to consider caveolinopathy in patients with incidental findings of creatine kinase elevation. NGS may be a useful method in the differential diagnosis of such cases.

Purpose: Caveolinopathy is a disease caused by caveolin-3 (CAV3) mutations that shows a wide clinical spectrum, including isolated hyperCKemia and limb-girdle muscular dystrophy. While recent advances in next-generation sequencing (NGS) have enabled earlier diagnosis of this disease, it remains difficult to predict the clinical course of each patient. Methods: This study summarizes the clinical presentations of 13 genetically confirmed caveolinopathy patients in four Korean families. Genetic diagnosis was performed using NGS technologies for probands and Sanger sequencing for the other family members. Results: Four coding mutations were found (p.Val103_Val104del, p.Asp28Glu, p.Pro105Leu, and p.Arg27Gln), and each family showed autosomal dominant inheritance. While all 13 cases had hyperCKemia, only five of them showed some myopathic features including ankle contracture, calf hypertrophy, exercise intolerance, and muscle cramping. This high proportion of asymptomatic cases suggests both that these mutations may be associated with a mild phenotype and that caveolinopathy may be an underdiagnosed disease. Conclusion: This study extends our understanding of caveolinopathy; in particular, the findings suggest the need to consider caveolinopathy in patients with incidental findings of creatine kinase elevation. NGS may be a useful method in the differential diagnosis of such cases. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical and imaging differences between limb⁃girdle muscular dystrophy type 2B (LGMD2B) and immune⁃mediated necrotizing myopathy (IMNM). Methods Forty⁃five patients with LGMD2B and 45 patients with IMNM from January 2014 to December 2018 were included. Sex, age of onset, age of diagnosis and time of delay in admission were recorded, and serum creatine kinase (CK) level was measured. Cervical flexion, proximal and distal upper limbs, proximal and distal lower limbs were evaluated by Medical Research Council (MRC) Level 6 and muscle strength percentages were calculated. Skeletal muscle fatty infiltration and edema degree on both thighs were evaluated by MRI. Results The onset age (Z=⁃3.605, P=0.000) and diagnosis age (Z=⁃2.757, P= 0.006) of LGMD2B patients were earlier than those of IMNM patients, while the delay time of admission was longer than that of IMNM patients (Z=⁃4.749, P=0.000), the serum CK was higher than that of IMNM patients (Z=⁃2.247, P=0.025). The muscle strength of neck flexion (Z=⁃6.320, P=0.000)and percentage of muscle strength(t=⁃6.320, P=0.000),the muscle strengh of proximal uppe rextremities (Z=⁃3.528, P= 0.000)and percentage of muscle strength (t=⁃3.762, P=0.000)in IMNM patients were lower than those in LGMD2B patients, while the muscle strengh of distal lower extremity (Z=⁃ 3.256, P=0.001) and percentage of muscle strength (t=⁃2.883, P=0.004) in LGMD2B patients were lower than those in IMNM patients. LGMD2B patients had higher muscle fatty infiltration degree in anterior group (Z=⁃3.119, P= 0.002)and posterior group (Z=⁃2.534, P=0.011)of thigh muscle than IMNM patients, but IMNM patients had highter thigh muscle edema degree in posterior group than LGMD2B patients (Z=⁃3.887, P=0.000). Conclusions Compared with IMNM patients, LGMD2B patients had earlier onset age, longer delay in diagnosis time, worse muscle strength of distal lower extremities, higher serum CK and more obviously thigh muscle fatty infiltration. In IMNM patients, muscle weakness of neck flexion and proximal upper extremities, thigh muscle edema of posterior group were more obvious. These characteristics contribute to the clinical differentiation of the two diseases. DOI：10.3969/j.issn.1672⁃6731.2020.09.004