Paramyotonia congenita: From clinical diagnosis to <i>in silico</i> protein modeling analysis

Nurputra, Dian Kesumapramudya; Nagao, Taku; Takeshima, Yasuhiro; Harahap, Indra Sari Kusuma; Morikawa, Satoru; Sakaeda, Toshiyuki; Lai, Poh San; Matsuo, Masafumi; Takaoka, Yutaka; Nishio, Hisahide

doi:10.1111/j.1442-200x.2012.03646.x

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…The R1448C mutation of SCN4A is commonly considered as the causative factor. This variant is consistent with epidemiological data from other countries [10] , [21] , [24] . According to previous studies, the most representative features of myotonia may be explained by the abnormal hyperexcitability of skeletal muscle induced by altered inactivation.…”

Section: Discussionsupporting

confidence: 91%

“…Structurally, the protein has four homologous domains (DI, DII, DIII, and DIV), each of which consists of six transmembrane alpha-helical segments (S1, S2, S3, S4, S5, and S6). The S4 segment in each domain contains from four to seven repeated three-residue motifs of a positively charged amino acid (usually arginine) followed by two hydrophobic amino acids [21] . The high concentration of positive charges in this alpha-helical segment suggests that the S4 segment is involved in voltage-dependent gating [5] .…”

Section: Discussionmentioning

confidence: 99%

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Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Huang

et al. 2015

Genomics Data

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Paramyotonia congenita (PC) is a rare autosomal dominant neuromuscular disorder characterized by juvenile onset and development of cold-induced myotonia after repeated activities. The disease is mostly caused by genetic mutations of the sodium channel, voltage-gated, type IV, alpha subunit (SCN4A) gene. This study intended to systematically identify the causative genetic variations of a Chinese Han PC family. Seven members of this PC family, including four patients and three healthy controls, were selected for whole exome sequencing (WES) using the Illumina HiSeq platform. Sequence variations were identified using the SoftGenetics program. The mutation R1448C of SCN4A was found to be the only causative mutation. This study applied WES technology to sequence multiple members of a large PC family and was the first to systematically confirm that the genetic change in SCN4A is the only causative variation in this PC family and the SCN4A mutation is sufficient to lead to PC.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Huang

et al. 2015

Genomics Data

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“…The mutation c.3938C>T (p.T1313M), which is the most frequently reported mutation in literature, was present in 2 of our families. This mutation is located in the DIII-DIV linker and is associated with classic characteristics of PMC: cold-and exercise-induced muscle stiffness as well as intermittent periods of weakness not necessarily related to cold or myotonia 12,13 . T1313 residue is located next to the COOHterminal end of the IFM motif, which is thought to serve as an inactivation particle that blocks the pore during fast inactivation 14 .…”

Section: Discussionmentioning

confidence: 99%

Paramyotonia congenita in a Slovak population: Genetic and pedigree analysis of 3 families

Cibulčík¹,

Špalek²,

Martinka³

et al. 2019

BIOMED PAP

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Background. Paramyotonia congenita is a non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. This condition cannot be distinguished on the basis of symptoms and signs alone. It requires consideration of genetics as more than 100 mutations in the CLCN1 gene and at least 20 mutations in the SCN4A gene are associated with the clinical features of the non-dystrophic myotonias. Only a few families with the described features but no genetic testing have been reported in Slovakia. This prompted us to investigate genetic mutations in the SCN4A gene in 3 Slovak families clinically diagnosed with paramyotonia. Subjects and Methods. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. SCN4A variants were screened by Sanger sequencing. Results. Our results revealed 2 potential disease-causing mutations present in the probands and affected family members-mutations c.3938C > T (p.T1313M) in two families and mutation c.2111C>T (p. T704M) in one family. Conclusion. Our results may help to identify genetic determinants as well as clarify genotype-phenotype relationships in patients with paramyotonia in Slovakia.

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“…These mutations were associated with classic characteristics of PC: cold-and exercise-induced muscle stiffness as well as intermittent periods of weakness not necessarily related to cold or myotonia. 9,18,[41][42][43] Functional experiments have shown that the mutations R1448H and T1313M impairs fast inactivation of sodium channels in a temperature-sensitive model, which may help explain the clinical phenotype of patients with PC who have these mutations. 44 Family 10 possessed a novel deletion (c.2638_2640delAAG); both the proband and his mother had this mutation.…”

Section: Discussionmentioning

confidence: 99%

“…4 More than 100 mutations in CLCN1 have been linked to MC, and more than 50 mutations have been identified in the SCN4A gene, of which about 20 have been linked to PC. 5 Most of these studies were conducted outside China, raising the question of how relevant they are to Chinese patients with MC, SCM, and PC. Indeed, in Chinese populations, fewer than 20 mutations in CLCN1 have been associated with MC [6][7][8][9][10][11] and only 8 mutations in SCN4A have been associated with SCM or PC.…”

Section: Introductionmentioning

confidence: 99%

Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature

Yang

et al. 2016

Channels

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Myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonias(SCM) were belonged to Non-dystrophic myotonias, in which muscle relaxation is delayed after voluntary or evoked contraction. These diseases can not be simply distinguished only based on symptoms and signs but also on genetics: more than 100 mutations in the CLCN1 gene have been associated with MC, while at least 20 mutations in the SCN4A gene have been associated with PC and SCM. Most of these genetics studies have been conducted outside China, only several MC, PC, and SCM families accepted gene scan were reported in China. Therefore we analyzed genetic mutations in CLCN1 and SCN4A in 10 Chinese families clinically diagnosed with Non-dystrophic myotonias. Our result revealed 12 potential disease-causing mutations(3 mutations were novel) that were present in the probands and affected family members. We also reviewed all available literature on mutations linked to these 3 disease in Chinese populations. Our results may help identify genetic determinants as well as clarify genotype-phenotype relationships.

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Paramyotonia congenita: From clinical diagnosis to in silico protein modeling analysis

Cited by 7 publications

References 30 publications

Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Paramyotonia congenita in a Slovak population: Genetic and pedigree analysis of 3 families

Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature

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