A de novo Mutation in the SCN4A Gene Causing Sodium Channel Myotonia

Ørstavik, Kristin; Wallace, Sean; Torbergsen, T.; Schöser, Benedikt; Tangsrud, Svein Erik; Kerty, Emı́lia; Rasmussen, Magnhild

doi:10.3233/jnd-150069

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…One potentially causative variant was identified in SCN4A in a 4 weeks old infant. SCN4A variants are described as cause of autosomal-dominant myotonia and periodic paralysis [ 32 ]. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity.…”

Section: Discussionmentioning

confidence: 99%

HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death

et al. 2021

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Background Molecular autopsy represents an efficient tool to save the diagnosis in up to one-third of sudden unexplained death (SUD). A defined gene panel is usually used for the examination. Alternatively, it is possible to carry out a comprehensive genetic assessment (whole exome sequencing, WES), which also identifies rare, previously unknown variants. The disadvantage is that a dramatic number of variants must be assessed to identify the causal variant. To improve the evaluation of WES, the human phenotype ontology (HPO) annotation is used internationally for deep phenotyping in the field of rare disease. However, a HPO-based evaluation of WES in SUD has not been described before. Methods We performed WES in tissue samples from 16 people after SUD. Instead of a fixed gene panel, we defined a set of HPO terms and thus created a flexible “virtual gene panel”, with the advantage, that recently identified genes are automatically associated by HPO terms in the HPO database. Results We obtained a mean value of 68,947 variants per sample. Stringent filtering ended up in a mean value of 276 variants per sample. Using the HPO-driven virtual gene panel we developed an algorithm that prioritized 1.4% of the variants. Variant interpretation resulted in eleven potentially causative variants in 16 individuals. Conclusion Our data introduce an effective diagnostic procedure in molecular autopsy of SUD with a non-specific clinical phenotype.

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Section: Discussionmentioning

confidence: 99%

HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death

et al. 2021

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“…One variant was identi ed in SCN4A in a four weeks old infant. SCN4A variants are described as cause of autosomal-dominant myotonia and periodic paralysis (25). Affected members developed in utero-or neonatal-onset muscle weakness of variable severity.…”

Section: Discussionmentioning

confidence: 99%

Dealing With Unspecific Clinical Phenotypes in Molecular Autopsy - HPO-Driven Whole Exome Sequencing Analysis Versus Gene Panel Testing

Schoen

Holzer²,

Laner

et al. 2020

Preprint

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Background: Molecular autopsy represents an efficient tool to save the diagnosis in up to one-third of sudden unexplained death (SUD). A defined gene panel is usually used for the examination. Alternatively, it is possible to carry out a comprehensive genetic assessment (Whole Exome Sequencing, WES), which also identifies rare, previously unknown variants. The disadvantage is that a dramatic number of variants must be assessed to identify the causal variant. To improve the evaluation of WES, the Human Phenotype Ontology (HPO) annotation is used internationally for deep phenotyping in the field of rare disease. However, a HPO-based evaluation of WES in SUD has not been described before.Methods: We performed WES in tissue samples from 16 people after SUD. Instead of a fixed gene panel, we defined a set of HPO terms and thus created a flexible “virtual gene panel”, with the advantage, that recently identified genes are automatically associated by HPO terms in the HPO database.Results: We obtained a median value of 68,947 variants per sample. Stringent filtering ended up in a median value of 276 variants per sample. Using the HPO-driven virtual gene panel we developed an algorithm that prioritized 1.4% of the variants. Variant interpretation resulted in eleven potentially causative variants in 16 individuals. Conclusion: Our data introduce an effective diagnostic procedure in molecular autopsy of SUD with a non-specific clinical phenotype.

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“…Several genes that have been previously studied in relation to pain show opposite changes in mRNA levels and their translation efficiency (spinal cord: Scn4a , Htr3b , Sprr1a , Rtn4rl2 , Tmem54 ; DRG: Myh7 , Mobp , 1500009C09Rik, Sall1 , Grin2b , Olig2 and 3110035E14Rik). For example, Scn4a gene codes for the alpha subunit of the voltage-dependent sodium channel, and mutations in this gene have been associated with sodium channel myotonia ( Orstavik et al, 2015 ). Htr3b codes for the serotonin-3B receptor.…”

Section: Discussionmentioning

confidence: 99%

Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain

Uttam

Wong

Amorim

et al. 2018

Neurobiology of Pain

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A de novo Mutation in the SCN4A Gene Causing Sodium Channel Myotonia

Cited by 5 publications

References 14 publications

HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death

HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death

Dealing With Unspecific Clinical Phenotypes in Molecular Autopsy - HPO-Driven Whole Exome Sequencing Analysis Versus Gene Panel Testing

Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain

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