Systematic analysis of SCN5A variants associated with inherited cardiac diseases

被引：0

作者：

Hermida, Alexis ^{[1
,2
,3
,4
,5
,6
,7
]}

Jedraszak, Guillaume ^{[2
,8
]}

Ader, Flavie ^{[9
,10
,11
]}

Denjoy, Isabelle ^{[11
,12
]}

Fressart, Veronique ^{[10
,11
]}

Maury, Phillipe ^{[13
]}

Beyls, Christophe ^{[1
]}

Bloch, Adrien ^{[9
,10
,11
]}

Clerici, Gaeel ^{[14
]}

Daire, Elise ^{[2
,15
]}

Defaye, Pascal ^{[16
]}

Dupin-Deguine, Delphine ^{[17
]}

Garcon, Loic ^{[2
,8
]}

Klug, Didier ^{[18
]}

Ginglinger, Emmanuelle ^{[4
,6
,19
]}

Hermida, Jean-Sylvain ^{[1
]}

Jesel, Laurence ^{[20
]}

Khraiche, Diala ^{[21
]}

Kubala, Maciej ^{[1
]}

Lacotte, Jerome ^{[22
]}

Laredo, Mikael ^{[3
,4
,5
,6
,7
,11
]}

Leenhardt, Antoine ^{[11
,12
]}

Le Guillou, Xavier ^{[23
]}

Lesaffre, Francois ^{[24
]}

Maltret, Alice ^{[25
]}

Magnin-Poull, Isabelle ^{[26
]}

Marijon, Eloi ^{[27
,28
]}

Nambot, Sophie ^{[29
]}

Neyroud, Nathalie ^{[11
]}

Ninni, Sandro ^{[18
]}

Palmyre, Aurelien ^{[30
,31
]}

Pasquie, Jean Luc ^{[32
,33
,34
]}

Proukhnitzky, Julie ^{[3
,4
,5
,6
,7
,11
]}

Reant, Patricia ^{[35
]}

Richard, Pascale ^{[10
,11
]}

Rollin, Anne ^{[13
]}

Rooryck, Caroline ^{[36
]}

Sacher, Frederic ^{[37
]}

Schaefer, Elise ^{[38
]}

Vernier, Agathe ^{[39
]}

Winum, Pierre-Francois ^{[40
]}

Wahbi, Karim ^{[41
]}

Waintraub, Xavier ^{[3
,4
,5
,6
,7
]}

Waldmann, Victor ^{[27
,28
]}

Weber, Sacha ^{[42
]}

Zouaghi, Amir ^{[43
]}

Charron, Philippe ^{[5
,6
,7
,11
,30
,31
]}

Extramiana, Fabrice ^{[11
,12
,44
]}

Gandjbakhch, Estelle ^{[3
,5
,7
,11
]}

机构：

[1] Amiens Picardie Univ Hosp, Cardiol Arrhythmia & Cardiac Stimulat Serv, Amiens, France

[2] Jules Verne Univ Picardie, HEMATIM EA4666, Amiens, France

[3] Hosp Pitie Salpetriere Inst Cardiol, AP HP, Inst Cardiol, Paris, France

[4] Hop La Pitie Salpetriere, AP HP, ICAN Inst Cardiometab & Nutr, Paris, France

[5] Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France

[6] Hop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, France

[7] Hop La Pitie Salpetriere, AP HP, Referral Ctr Hereditary Cardiac Dis, Paris, France

[8] Amiens Picardie Univ Hosp, Mol Genet Lab, Amiens, France

[9] UFR Pharm, Fac Sante, Dept Sci Biol & Med, Unite Pedag Biochim, F-75006 Paris, France

[10] Sorbonne Univ, Pitie Salpetriere Charles Foix, AP HP, Serv Biochim Metab,DMU Biogem,Unite Fonct Cardioge, Paris, France

[11] Sorbonne Univ, Res Unit Cardiovasc & Metab Dis, INSERM, UMRS 1166, Paris, France

[12] Hop Bichat Claude Bernard, AP HP, CNMR Malad Cardiaques Hereditaires Rares, Paris, France

[13] Cte Hosp Univ, Serv Cardiol, TOULOUSE, France

[14] Ctr Hosp Univ, Serv Cardiol, St Pierre, La Reunion, France

[15] CHU Amiens, Serv Pediat, Amiens, France

[16] Ctr Hosp Univ, Serv Cardiol, Grenoble, France

[17] CHU Toulouse, Serv Genet, Toulouse, France

[18] France CHU Lille, Inst Pasteur Lille, Serv Cardiol, CHU Lille, F-59000 Lille, France

[19] CH Mulhouse, Serv Genet, Mulhouse, France

[20] CHU Strasbourg, Serv Cardiol, Strasbourg, France

[21] Hop Necker Enfants Malad, AP HP, Pediat, Paris, France

[22] Inst Jacques Cartier, Serv Cardiol, Massy, France

[23] CHU Poitiers, Serv Genet Med, Poitiers, France

[24] CHU Reims, Serv Cardiol, Reims, France

[25] GHPSJ Hop Marie Lannelongue, Serv Cardiopathie Congenitale, Le Plessis Robinson, France

[26] CHU Nancy, Serv Cardiol, Nancy, France

[27] Hop Europeen Georges Pompidou, AP HP, Serv Cardiol, Paris, France

[28] Univ Paris Cite, INSERM, PARCC, Paris, France

[29] Hop Enfants, Ctr Reference Anomalies Dev & Syndromes Malformati, FHU TRANSLAD, Dijon, France

[30] Ambroise Pare Hosp, AP HP, Dept Genet, F-92100 Boulogne Billancourt, France

[31] Ambroise Pare Hosp, AP HP, Referral Ctr Cardiac Hereditary Cardiac Dis, Boulogne Billancourt, France

[32] CHU Montpellier, Serv Cardiol, Montpellier, France

[33] Univ Montpellier, PhyMedExp, INSERM U1046, Montpellier, France

[34] CHU Montpellier, Montpellier, France

[35] Univ Bordeaux, Bordeaux Univ Hosp, Serv Cardiol,Referral Ctr Rare & Inherited Cardiom, Bordeaux, France

[36] CHU Bordeaux, Serv Genet Med, Bordeaux, France

[37] Univ Bordeaux, Bordeaux Univ Hosp, Bordeaux Univ Hosp, Serv Rythmol,CRMR Cardiogen,ERN Guard Heart,INSERM, Bordeaux, France

[38] CHU Strasbourg, Inst Genet Med Alsace, Serv Genet Med, Strasbourg, France

[39] Victor Pauchet Clin, Amiens, France

[40] CHU Nimes, Serv Cardiol, Nimes, France

[41] CHU Cochin, AP HP, Serv Cardiol, Paris, France

[42] CHU Caen, Serv Genet, Caen, France

[43] CH Antibes, Serv Cardiol, Antibes, France

[44] Univ Paris Cite, Paris, France

来源：

HEART RHYTHM | 2025年 / 22卷 / 03期

关键词：

Domains; Overlap syndrome; Phenotypes; Pleiotropy; SCN5A; LONG QT SYNDROME; BRUGADA-SYNDROME; CONDUCTION DEFECTS; MUTATION; PHENOTYPE; TYPE-3;

D O I：

10.1016/j.hrthm.2024.08.018

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes or pleiotropy, which have not been systematically described. In addition, the involvement of SCN5A in dilated cardiomyopathies (DCMs) remains controversial. OBJECTIVE We aimed to evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and to determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced with a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS The study included 170 P/LP variants found in 495 patients. Of them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, 6 with progressive cardiac conduction disease, 4 with multifocal ectopic Purkinje-related premature contractions, and 3 with sick sinus syndrome. Thirtytwo variants (19%) were associated with overlap syndromes or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Of those, 8 were carried by 8 patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960) if not questionable.

引用

页码：844 / 851

页数：8

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