Identification of novel mutations of the<i>CLCN1</i>gene for myotonia congenital in China

Meng, Yanxin; Zhao, Zhe; Shen, Hongrui; Qi, Bing; Hu, Jing

doi:10.1080/01616412.2015.1114741

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…In our study, PMC with the L689F variant was accompanied by progressive muscle weakness, which was characterized by difficulty in climbing stairs, and similar muscle weakness has been reported for the same variant ( 7 ). In eight patients, myotonia could cause secondary dystonia, which could lead to secondary joint contractures during the development of the disease ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Sequencing showed that 19 different pathogenic variants in the CLCN1 gene were identified in 17 MC patients, including 14 missense, four frameshift, and one non-sense variants. Among them, c.795T>G (p.D265E) was a novel missense variant, and the other 18 variants had previously been reported (6,12,(15)(16)(17). Combining this with family history, 10 patients with one heterozygous variant and seven patients with two compound heterozygous variants were diagnosed with DMC and RMC, respectively.…”

Section: Genetic Analysismentioning

confidence: 94%

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The Clinical, Myopathological, and Genetic Analysis of 20 Patients With Non-dystrophic Myotonia

et al. 2022

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IntroductionNon-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations. This study aimed to describe the clinical, myopathological, and genetic analysis of NDM in a large Chinese cohort.MethodsWe reviewed the clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, genetic analysis, treatment, and follow-up of 20 patients (from 18 families) with NDM.ResultsCases included myotonia congenita (MC, 17/20) and paramyotonia congenita (PMC, 3/20). Muscle stiffness and hypertrophy, grip and percussion myotonia, and the warm-up phenomenon were frequently observed in MC and PMC patients. Facial stiffness, eye closure myotonia, and cold sensitivity were more common in PMC patients and could be accompanied by permanent weakness. Nine MC patients and two PMC patients had cardiac abnormalities, mainly manifested as cardiac arrhythmia, and the father of one patient died of sudden cardiac arrest. Myotonic runs in electromyography were found in all patients, and seven MC patients had mild myopathic changes. There was no difference in muscle pathology between MC and PMC patients, most of whom had abnormal muscle fiber type distribution or selective muscle fiber atrophy. Nineteen CLCN1 variants were found in 17 MC patients, among which c.795T>G (p.D265E) was a new variant, and two SCN4A variants were found in three PMC patients. The patients were treated with mexiletine and/or carbamazepine, and the symptoms of myotonia were partially improved.ConclusionsMC and PMC have considerable phenotypic overlap. Genetic investigation contributes to identifying the subtype of NDM. The muscle pathology of NDM lacks specific changes.

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Analysismentioning

confidence: 94%

The Clinical, Myopathological, and Genetic Analysis of 20 Patients With Non-dystrophic Myotonia

et al. 2022

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“…While some researchers reported that cardiac abnormalities such as accompanying arrhythmia, pre-excitation syndrome, or left ventricular enlargement were observed in cases with MC 10 but others reported that there was no cardiac problem in cases with MC 11 , 12 . According to inheritance pattern of the disease, family members of our case also had c.1886T>C, (p.Leu629Pro) alteration in CLCN1 gene with autosomal recessive congenital myotonia, too.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cases With Myotonia Congenita for Cardiovascular Risk

Damar¹,

Eröz²

2019

MMJ

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Objective: Myotonia Congenita (MC) is a hereditary neuromuscular disorder caused by a mutation in chloride voltage-gated channel 1 (CLCN1) gene. The incidence of MC is estimated as 1 in 100.000. The absence of left main coronary artery (LMCA) is a rare coronary anomaly. Here we present a family with four members who have MC variation carrier and cardiovascular risk. Method: The demographic features, laboratory findings, anthropometric measurements and cardiological examination of the cases were recorded. In addition, CLCN1 gene was sequenced by NGS (Next Generation Sequencing Method) and possible causes of inherited thrombophilia risk including MTHFR (A1298C), Factor V Leiden (G1691A), Factor II (G20210A), MTHFR (C677T), Factor V Cambridge (G1091C), plasminogen activator inhibitor 1 (PAI-1) 4G/5G, APOE, APOB, ITGB, ACE (ins/del), FVHR2 and FGB gene alterations were evaluated. Results: Case 1 had homozygous c.1886T>C (p.Leu629Pro) alteration in CLCN1 gene and also coronary artery disease, myocardial infarction (MI) history, hyperlipidemia, primary hypertension, vertigo, lomber disc herniation and hearing loss. LMCA was not detected in coronary angiography in Case 1. Cases 2, 3 and 4 had heterozygous c.1886T>C (p.Leu629Pro) alteration with normal electrocardiographic and echocardiographic findings. Additionally, all of family members had genetic risk factors for the related gene, which lead to an increased risk of cardiovascular disease. Conclusion: Since alteration of chloride channels in cardiomyocytes leads to variable myocardial involvement, cases with MC should be regularly followed for cardiovascular risk. Moreover, the cases with MC and with genetic profile associated with high cardiovascular risk should also be regularly followed up by cardiologists.

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“…It would be interesting to functionally analyze stop codon-forming mutations beyond Y686*, as this could provide evidence of the location in which the protein starts being functional. A clue about this is provided by the mutation Q788*: although it has not been functionally characterized, it was described that it behaves in a dominant manner [50], likely due to a dominant-negative effect, where the full ClC-1 structure is modified by the interaction of wild-type ClC-1 and an altered ClC-1 structure, affecting thereby the chloride conductance in the patients.…”

Section: Channel Disruptionmentioning

confidence: 99%

ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations

Brenes,

Pusch,

Morales

2023

Biomedicines

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Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (CLCN1) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The biophysical properties of the mutated channel have been explored and analyzed through in vitro approaches, providing important clues to the general function/dysfunction of the wild-type and mutated channels. After an exhaustive search for CLCN1 mutations, we report in this review more than 350 different mutations identified in the literature. We start discussing the physiological role of the ClC-1 channel in skeletal muscle functioning. Then, using the reported functional effects of the naturally occurring mutations, we describe the biophysical and structural characteristics of the ClC-1 channel to update the knowledge of the function of each of the ClC-1 helices, and finally, we attempt to point out some patterns regarding the effects of mutations in the different helices and loops of the protein.

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Identification of novel mutations of theCLCN1gene for myotonia congenital in China

Cited by 8 publications

References 10 publications

The Clinical, Myopathological, and Genetic Analysis of 20 Patients With Non-dystrophic Myotonia

The Clinical, Myopathological, and Genetic Analysis of 20 Patients With Non-dystrophic Myotonia

Evaluation of Cases With Myotonia Congenita for Cardiovascular Risk

ClC-1 Chloride Channel: Inputs on the Structure–Function Relationship of Myotonia Congenita-Causing Mutations

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