WEKO3
アイテム
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CaM variants may present with early-onset long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, or sudden cardiac death. Most reported variants occurred de novo. We identified a novel CALM3 variant, p.Asn138Lys (N138K), in a 4-generation family segregating with LQTS. The aim of this study was to elucidate its pathogenicity and to compare it with that of p.D130G-CaM—a variant associated with a severe LQTS phenotype.", "subitem_description_type": "Abstract"}, {"subitem_description": "Methods:\nWe performed whole exome sequencing for a large, 4-generation family affected by LQTS. To assess the effect of the detected CALM3 variant, the intrinsic Ca2+-binding affinity was measured by stoichiometric Ca2+ titrations and equilibrium titrations. L-type Ca2+ and slow delayed rectifier potassium currents (ICaL and IKs) were recorded by whole-cell patch-clamp. Cav1.2 and Kv7.1 membrane expression were determined by optical fluorescence assays.", "subitem_description_type": "Abstract"}, {"subitem_description": "Results:\nWe identified 14 p.N138K-CaM carriers in a family where 2 sudden deaths occurred in children. Several members were only mildly affected compared with CaM-LQTS patients to date described in literature. The intrinsic Ca2+-binding affinity of the CaM C-terminal domain was 10-fold lower for p.N138K-CaM compared with wild-type-CaM. ICaL inactivation was slowed in cells expressing p.N138K-CaM but less than in p.D130G-CaM cells. Unexpectedly, a larger IKs current density was observed in cells expressing p.N138K-CaM, but not for p.D130G-CaM, compared with wild-type-CaM.", "subitem_description_type": "Abstract"}, {"subitem_description": "Conclusions:\nThe p.N138K CALM3 variant impairs Ca2+-binding affinity of CaM and ICaL inactivation but potentiates IKs. 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"nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-6125-0789"}]}, {"creatorNames": [{"creatorName": "ISBELL, Holly M."}], "nameIdentifiers": [{"nameIdentifier": "8942", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "0000-0002-4055-2016", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-4055-2016"}]}, {"creatorNames": [{"creatorName": "FRESSART, Véronique"}], "nameIdentifiers": [{"nameIdentifier": "8943", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "0000-0003-4749-1428", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-4749-1428"}]}, {"creatorNames": [{"creatorName": "DENJOY, Isabelle"}], "nameIdentifiers": [{"nameIdentifier": "8944", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "0000-0002-1786-9461", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-1786-9461"}]}, {"creatorNames": [{"creatorName": "DEBBICHE, Amal"}], 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Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family
http://hdl.handle.net/10422/00013274
http://hdl.handle.net/10422/00013274567cfbb7-fd8e-4a5a-a11f-27a73df5fb40
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-04-08 | |||||
タイトル | ||||||
タイトル | Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | calmodulin | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | ion channels | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | long QT syndrome | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | phenotype | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | potassium | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
KATO, Koichi
× KATO, Koichi× ISBELL, Holly M.× FRESSART, Véronique× DENJOY, Isabelle× DEBBICHE, Amal× ITOH, Hideki× POINSOT, Jacques× GEORGE Jr, Alfred L.× COULOMBE, Alain× SHEA, Madeline A.× GUICHENEY, Pascale |
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著者別名 |
加藤, 浩一
× 加藤, 浩一× 伊藤, 英樹 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: CaM (calmodulin), encoded by 3 separate genes (CALM1, CALM2, and CALM3), is a multifunctional Ca2+-binding protein involved in many signal transduction events including ion channel regulation. CaM variants may present with early-onset long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, or sudden cardiac death. Most reported variants occurred de novo. We identified a novel CALM3 variant, p.Asn138Lys (N138K), in a 4-generation family segregating with LQTS. The aim of this study was to elucidate its pathogenicity and to compare it with that of p.D130G-CaM—a variant associated with a severe LQTS phenotype. |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Methods: We performed whole exome sequencing for a large, 4-generation family affected by LQTS. To assess the effect of the detected CALM3 variant, the intrinsic Ca2+-binding affinity was measured by stoichiometric Ca2+ titrations and equilibrium titrations. L-type Ca2+ and slow delayed rectifier potassium currents (ICaL and IKs) were recorded by whole-cell patch-clamp. Cav1.2 and Kv7.1 membrane expression were determined by optical fluorescence assays. |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Results: We identified 14 p.N138K-CaM carriers in a family where 2 sudden deaths occurred in children. Several members were only mildly affected compared with CaM-LQTS patients to date described in literature. The intrinsic Ca2+-binding affinity of the CaM C-terminal domain was 10-fold lower for p.N138K-CaM compared with wild-type-CaM. ICaL inactivation was slowed in cells expressing p.N138K-CaM but less than in p.D130G-CaM cells. Unexpectedly, a larger IKs current density was observed in cells expressing p.N138K-CaM, but not for p.D130G-CaM, compared with wild-type-CaM. |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Conclusions: The p.N138K CALM3 variant impairs Ca2+-binding affinity of CaM and ICaL inactivation but potentiates IKs. The variably expressed phenotype of this variant compared with previously published de novo LQTS-CaM variants is likely explained by a milder impairment of ICaL inactivation combined with IKs augmentation. |
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書誌情報 |
en : Circulation. Arrhythmia and electrophysiology 巻 15, 号 3, p. e010572, 発行日 2022-03 |
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出版者 | ||||||
出版者 | Lippincott Williams & Wilkins | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1941-3084 | |||||
PMID | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 35225649 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1161/CIRCEP.121.010572 | |||||
関連名称 | 10.1161/CIRCEP.121.010572 | |||||
権利 | ||||||
権利情報 | © 2022 American Heart Association, Inc | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |