Clinicopathological‐genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre

Huang, Kun; Duan, Hui-Qian; Li, Qiu‐Xiang; Luo, Yue‐Bei; Bi, Fangfang; Yang, Huan

doi:10.1111/jcmm.17417

Cited by 7 publications

(8 citation statements)

References 57 publications

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“…Muscle samples were immediately frozen in isopentane, cooled with liquid nitrogen, and stored at −80°C. Immunohistochemical staining was performed as described previously with minor modifications ( 17 – 20 ). Briefly, histological and immunohistochemical analyses were performed on 8 μm-thick frozen sections prepared using a cryostat.…”

Section: Methodsmentioning

confidence: 99%

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center

Huang

Duan

et al. 2022

Front. Neurol.

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BackgroundGlycogen storage disease (GSDs) is characterized by abnormally inherited glycogen metabolism. GSD IXd, which is caused by mutations in the PHKA1 gene, is an X-linked rare disease with mild myopathic symptoms. To date, only 13 patients with GSD IXd have been reported. In this study, we aimed to expand the clinicopathological-genetic spectrum of GSD IXd at a neuromuscular center in China.MethodsData on patients diagnosed with GSD IXd at our neuromuscular center were collected retrospectively. Clinical features, electrophysiology, muscle pathology, and genetic information were analyzed.ResultsBetween 2015 and 2021, three patients were diagnosed with GSD IXd based on clinical manifestations, pathological findings, and genetic testing. One patient presented with mitochondrial myopathy. All patients exhibited muscle weakness and elevated levels of creatine kinase. Electromyography-detected myopathic changes were found in two patients, whereas one patient refused to undergo this examination. Pathological examinations in all patients revealed subsarcolemmal accumulation of glycogen under PAS staining. All patients had mutations in the PHKA1 gene and the patient with mitochondrial myopathy also had a mutation in the MT-TL1 gene.ConclusionOur study expands the clinicogenotype and phenotype of GSD IXd in a Chinese population. Our study also expands the known mutation spectrum for GSD IXd, contributing to a better characterization and understanding of this ultrarare neuromuscular disorder.

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Section: Methodsmentioning

confidence: 99%

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center

Huang

Duan

et al. 2022

Front. Neurol.

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“…Pathological examinations were performed as described elsewhere with minor modifications [ 22 – 25 ]. Briefly, TA muscles of mouse were snap-frozen in isopentane chilled with liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

Calcitriol increases MBNL1 expression and alleviates myotonic dystrophy phenotypes in HSALR mouse models

Huang

Wang

et al. 2022

J Transl Med

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Background Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3′ untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1. Methods All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice. Results In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells. Conclusion Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.

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“…SCN4A -CMS has been reported in 6 patients since 2003 [ 79 , 80 , 81 , 140 , 270 , 274 ]. SCN4A -CMS shows frequent episodes of respiratory arrest, bulbar paralysis, and muscle weakness that persist 30 to 60 min.…”

Section: Thirty-five Genes In 14 Groups Of Cmsmentioning

confidence: 99%

“…Analysis of 278 patients with sudden infantile death syndrome (SIDS) revealed 4 patients with SCN4A -CMS [ 5 ]. ChEIs are either effective [ 79 , 142 , 274 ] or ineffective [ 270 ]. In addition, a SCN4A-CMS patient showed marked cholinergic adverse effects with a small amount of ChEI [ 80 ].…”

Section: Thirty-five Genes In 14 Groups Of Cmsmentioning

confidence: 99%

“…AGRN -CMS has been reported in 13 original articles since 2009 [ 6 , 141 , 142 , 274 , 275 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 ]. Two patients with AGRN -CMS reported in 2009 were 42-year-old female and 36-year-old male in a single pedigree, who had mild limb muscle weakness and unilateral ptosis since childhood [ 285 ].…”

Section: Thirty-five Genes In 14 Groups Of Cmsmentioning

confidence: 99%

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Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

Ohno

Ohkawara

Shen

et al. 2023

IJMS

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Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS (AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MUSK, MYO9A, PLEC, PREPL, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TOR1AIP1, UNC13A, VAMP1). The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. Measurement of compound muscle action potentials elicited by repetitive nerve stimulation is required to diagnose CMS. Clinical and electrophysiological features are not sufficient to identify a defective molecule, and genetic studies are always required for accurate diagnosis. From a pharmacological point of view, cholinesterase inhibitors are effective in most groups of CMS, but are contraindicated in some groups of CMS. Similarly, ephedrine, salbutamol (albuterol), amifampridine are effective in most but not all groups of CMS. This review extensively covers pathomechanical and clinical features of CMS by citing 442 relevant articles.

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Clinicopathological‐genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre

Cited by 7 publications

References 57 publications

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center

Calcitriol increases MBNL1 expression and alleviates myotonic dystrophy phenotypes in HSALR mouse models

Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

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