疾患詳細

疾患詳細





#113900
Progressive familial heart block, type IA (PFHB1A)
(PFHBIA)
(Heart block, progressive familial, type I; PFHBI)
(Lenegre-Lev disease)
(Cardiac conduction defect, progressive; PCCD)
(Bundle branch block)
(Hereditary bundle branch system defect; HBBD)
(Heart block, nonprogressive, included)
(Cardiac conduction defect, nonprogressive, included)

進行性家族性心ブロック IA 型
(心ブロック, 進行性家族性, I 型)
(Lenegre-Lev 病)
(心伝導障害, 進行性; PCCD)
(脚ブロック)
(遺伝性脚ブロック; HBBD)
(心ブロック, 非進行性)
(心伝導障害, 非進行性)

責任遺伝子:600163 Sodium channel, voltage-gated, type V, alpha peptide (SCN5A) <3p22.2>
遺伝形式:常染色体優性

(症状)
(GARD)
 <30%-79%>
 Arrhythmia (不整脈) [HP:0011675] [01700]
 
 
 Autosomal dominant inheritance (常染色体優性遺伝) [HP:0000006]
 Complete heart block with broad QRS complexes (幅広いQRS複合を伴う完全心ブロック) [HP:0005170] [01700]
 Dyspnea (呼吸困難) [HP:0002094] [01606]
 Left anterior fascicular block (左前分枝ブロック) [HP:0011711] [01700]
 Left posterior fascicular block (左後分枝ブロック) [HP:0005172] [01700]
 Right bundle branch block (右脚ブロック) [HP:0011712] [01700]
 Sudden cardiac death (突然死) [HP:0001645] [0115]
 Sudden death (突然死) [HP:0001699] [0115]
 Syncope (失神) [HP:0001279] [0151]

(UR-DBMS)
【一般】呼吸困難
 失神エピソード
 Stokes-Adams 発作
 突然死
 心房性不整脈
 心室性期外収縮
 Wolff-Parkinson-White 症候群
【心】脚ブロック
 右脚ブロック
 左前脚または後脚半ブロック
 幅広い RS 波を伴う完全心ブロック
【その他】遺伝的異質性 (604559参照)

(責任遺伝子) *600163 Sodium channel, voltage-gated, type V, alpha peptide (SCN5A) <3p22.2>
(1) Long QT syndrome 3 (603830 AD)
.0001 Long QT syndrome 3 [SCN5A, 9-BP DEL, NT4661 [dbSNP:rs397514251] (RCV000009962...) (Wang et al. 1995; Clancy and Rudy 1999)
.0002 Long QT syndrome 3 [SCN5A, ARG1644HIS] (dbSNP:rs28937316) (ExAC:rs28937316) (RCV000009963...)(Wang et al. 1995)
.0003 Long QT syndrome 3 [SCN5A, ASN1325SER] (dbSNP:rs28937317) (RCV000058618...) (Wang et al. 1995)
.0007 Long QT syndrome 3 [SCN5A, ARG1623GLN [dbSNP:rs137854600] (RCV000009970...) (Long QT syndrome 3/6, digenic, included) (Makita et al. 1998; Kambouris et al. 2000; Millat et al. 2006)
.0008 Long QT syndrome 3 [SCN5A, GLU1784LYS [dbSNP:rs137854601](RCV000009972...) (Brugada syndrome, included) (Sinus nose disease, included) (Wei et al. 1999)
.0013 Long QT syndrome 3 [SCN5A, 3-BP INS, 5537TGA [dbSNP:rs397514449] (RCV000009979...) (Brugada syndrome, included) (Bezzina et al. 1999)
.0015 Long QT syndrome 3 [SCN5A, SER941ASN [dbSNP:rs137854605] (RCV000009982) (Schwartz et al. 2000)
.0019 Long QT syndrome 3 [SCN5A, ALA997SER [dbSNP:rs137854609] (ExAC:rs137854609) (RCV000058542...) (Ackerman et al. 2001)
.0020 Long QT syndrome 3 [SCN5A, ARG1826HIS [dbSNP:rs137854610] (ExAC:rs137854610) (RCV000154827...) (Ackerman et al. 2001)
.0029 Long QT syndrome 3 [SCN5A, TYR1795CYS [dbSNP:rs137854614] (RCV000058778...) (Rivolta et al. 2001)
.0035 Long QT syndrome 2/3, digenic [SCN5A, ASP1819ASN [dbSNP:rs137854619] (ExAC:rs137854619) (RCV000010005...) (Millat et al. 2006)
(2) Brugada syndrome 1 (601144 AD)
.0004 Brugada syndrome 1 [SCN5A, ARG1232TRP AND THR1620MET [dbSNP:rs199473282] [dbSNP:rs199473207] (ExAC:rs199473282) (RCV000183042...) (Chen et al. 1998; Dumaine et al. 1999; Makita et al. 2000)
.0005 Brugada syndrome 1 [SCN5A, IVS7DS, 2-BP INS [dbSNP:rs397514252] (RCV000009966) (Chen et al. 1998)
.0006 Brugada syndrome 1 [SCN5A, 1-BP DEL, VAL1398TER [dbSNP:rs397514446] (RCV000009967) (Chen et al. 1998)
.0011 Brugada syndrome 1 [SCN5A, ARG1512TRP [dbSNP:rs137854602] (ExAC:rs137854602) (RCV000222521...) (Rook et al. 1999)
.0012 Brugada syndrome 1 [SCN5A, ALA1924THR [dbSNP:rs137854603] (ExAC:rs137854603) (RCV000009978...) (Rook et al. 1999)
.0021 Brugada syndrome 1 [SCN5A, ARG367HIS] (dbSNP:rs28937318) (RCV000182958...) (Vatta et al. 2002)
.0022 Brugada syndrome 1 [SCN5A, ALA735VAL [dbSNP:rs137854611] (ExAC:rs137854611) (RCV000009989...) (Vatta et al. 2002)
.0023 Brugada syndrome 1 [SCN5A, ARG1192GLN] (dbSNP:rs41261344) (ExAC:rs41261344) (RCV000009990...) (Long QT syndrome 3, aquired, susceptibility to, included) (Vatta et al. 2002)
.0030 Brugada syndrome 1 [SCN5A, TYR1795HIS [dbSNP:rs137854615] (RCV000009999...) (Rivolta et al. 2001)
.0032 Brugada syndrome 1 [SCN5A, GLY1262SER [dbSNP:rs137854616] (ExAC:rs137854616) (RCV000058602...) (Shin et al. 2004)
.0033 Brugada syndrome 1 [SCN5A, GLU1053LYS [dbSNP:rs137854617] (Mohler et al. 2004; Darbar et al. 2008)
.0036 Brugada syndrome 1 [SCN5A, TRP1421TER [dbSNP:rs137854620] (RCV000010006) (Niu et al. 2006)
.0040 Brugada syndrome 1 [SCN5A, VAL232ILE and LEU1308PHE [dbSNP:rs41313031] [dbSNP:rs45471994] (ExAC:rs41313031) (ExAC:rs45471994) (RCV000243761...) (Barajas-Martinez et al. (2008)
(3) Progressive familial heart block, type IA (113900)
.0009 Progressive familial heart block, type IA [SCN5A, IVS22DS, T-C, +2 [dbSNP:rs397514447](RCV000009975) (Schott et al. 1999)
.0017 Progressive familial heart block, type IA [SCN5A, ASP1595ASN [dbSNP:rs137854607] (RCV000058705...) (Wang et al. 2002)
.0018 Progressive familial heart block, type IA [SCN5A, GLN298SER [dbSNP:rs137854608] (ExAC:rs137854608) (RCV000009985...) (Wang et al. 2002)
.0031 Progressive familial heart block, type IA [SCN5A, THR512ILE AND HIS558ARG [dbSNP:rs199473118] [dbSNP:rs1805124](ExAC:rs199473118) (ExAC:rs1805124) (RCV000304709...) (Viswanathan et al. 2003; Darbar et al. 2008)
(4) Heart block, nonprogressive (113900)
.0010 Heart block, nonprogressive [SCN5A, 1-BP DEL, 5280G [dbSNP:rs3975144485280G] (RCV000009976) (Schott et al. 1999)
(5) Ventricular fibrillation, idiopathic (603829)
.0014 Ventricular fibrillation, idiopathic [SCN5A, SER1710LEU [dbSNP:rs13785] (ExAC:rs137854604) (RCV000058743...) (Akai et al. 2000)
(6) Cardiac conduction defect, nonprogressive (115080)
.0016 Cardiac conduction defect, nonprogressive [SCN5A, GLY514CYS [dbSNP:rs137854606] (RCV000009984...) (Tan et al. 2001)
(7) Long QT syndrome 3, aquired, susceptibility to
.0024 Long QT syndrome 3, aquired, susceptibility to [SCN5A, SER1102TYR] (dbSNP:rs7626962) (ExAC:rs7626962) (RCV000396768...) (Sudden infant death syndrome, included) (Splawski et al. 2002; Chen et al. 2002; Plant et al. 2006; Darbar et al. 2008)
(8) Sick sinus syndrome 1, autosomal recessice (608567)
.0025 Sick sinus syndrome 1, autosomal recessice [SCN5A, PRO1298LEU [dbSNP:rs28937319] (RCV000058612...) (Benson et al. 2003)
.0026 Sick sinus syndrome 1, autosomal recessice [SCN5A, GLY1408ARG [dbSNP:rs137854612] (RCV000058649...) (Brugada syndrome, included) (Cardiac conduction defect, included) (Benson et al. 2003; Kyndt et al. 2001)
.0027 Sick sinus syndrome 1, autosomal recessice [SCN5A, THR220ILE] (dbSNP:rs45620037) (ExAC:rs45620037) (RCV000258831...) (Benson et al. 2003)
.0028 Sick sinus syndrome 1, autosomal recessice [SCN5A, ARG1623TER [dbSNP:rs137854613](ExAC:rs137854613) (RCV000183087...) (Benson et al. 2003)
(9) Cardiomyopathy, dilated, 1E (601154); Atrial standstill 1 (108770)
.0034 Cardiomyopathy, dilated, 1E [SCN5A, ASP1275ASN [dbSNP:rs137854618] (RCV000058604...) (108770 Atrial standstill, included) (McNair et al. 2004; Groenewegen et al. 2003)
.0037   MOVED TO 600163.0027
.0038 Cardiomyopathy, dilated, 1E [SCN5A, 2-BP INS, NT2550 [dbSNP:rs397514450] (RCV000010008...) (Olson et al. 2005
.0039 Cardiomyopathy, dilated, 1E [SCN5A, ASP1595HIS [dbSNP:rs137854607] (RCV000058706...) (Olson et al. 2005)
.0046 Cardiomyopathy, dilated, 1E [SCN5A, ARG222GLN (rs45546039) [dbSNP:rs45546039] (v) (Hershberger et al. 2008; Laurent et al. 2012;Nair et al. (2012; Mann et al. 2012)
.0047 Cardiomyopathy, dilated, 1E [SCN5A, ILE1835THR [dbSNP:rs45563942] (ExAC:rs45563942) (RCV000032640...) (Hershberger et al. 2008)
.0048 Atrial standstill 1, digenic [SCN5A, LEU212PRO [dbSNP:rs199473070] (RCV000114993...) (Makita et al. 2005)
(10) Atrial fibrillation, familial, 10 (614022)
.0041 Atrial fibrillation, familial, 10 [SCN5A, ASN1986LYS [dbSNP:rs199473335] (ExAC:rs199473335) (RCV000148858...) (Ellinor et al. 2008)
.0042 Atrial fibrillation, familial, 10 [SCN5A, HIS445ASP [dbSNP:rs199473112] (ExAC:rs199473112) (RCV000022948...) (Darbar et al. 2008)
.0043 Atrial fibrillation, familial, 10 [SCN5A, ASN470LYS [dbSNP:rs199473115] (RCV000058421...) (Darbar et al. 2008)
.0044 Atrial fibrillation, familial, 10 [SCN5A, GLU428LYS [dbSNP:rs199473111] (ExAC:rs199473111) (RCV000058411...) (Darbar et al. 2008)
.0045 Atrial fibrillation, familial, 10 [SCN5A, GLU655LYS [dbSNP:rs199473579](RCV000058468...) (Darbar et al. 2008)

(ノート)
●(#) は、この型の進行性家族性心ブロック I 型 (PFHB1A) は、3p21 の SCN5A 遺伝子 (600163)の変異が原因でありうるため

●進行性家族性心ブロック I 型 (PFHBI, PFHB1) は、常染色体優性の心脚疾患で、完全心ブロックへ進行しうる (Brink and Torrington, 1977; van der Merwe et al., 1986; van der Merwe et al., 1988)
 心電図で脚疾患の証拠により定義される
 →幅広いQRS複合を伴う、右脚ブロック、左前または後束枝ブロック、または完全ブロック
 進行は、正常心電図から右脚ブロックへ、および、右脚ブロックから完全心ブロックへとみられる
 これらの心電図の特徴は、進行性家族性心ブロック II 型 (PFHBII, PFHB2; 140400)から I 型を区別する
 → II 型では、完全心ブロックの発症は、狭いQRS複合を伴う
 心電図的には、各々、脚ブロック (PFHB1) と房室ブロックと本態性補充調律を伴う房室結節ブロック (PFHB2)が特徴である
 PFHBI は、 完全心ブロックが呼吸困難、失神エピソードまたは突然死のいずれかを併発する時に症状としてみられる
 治療としては、定期的心電図経過により最もよく管理し、時宜がかなったペースメーカーの埋め込みである (Brink et al., 1995)

Genetic Heterogeneity of Progressive Familial Heart Block Type I
Progressive familial heart block type IB (PFHB1B; 604559) is caused by mutation in the TRPM4 gene (606936) on chromosome 19q13.32.

▼ Clinical Features
Progressive cardiac conduction defect (PCCD), also called Lenegre-Lev disease (Lenegre, 1964; Lev et al., 1970), is one of the most common cardiac conduction disturbances. It is characterized by progressive alteration of cardiac conduction through the His-Purkinje system with right or left bundle branch block and widening of QRS complexes, leading to complete atrioventricular block and causing syncope and sudden death. It represents the major cause of pacemaker implantation in the world (0.15 implantations per 1,000 inhabitants per year in developed countries). PCCD is considered a primary degenerative disease or an exaggerated aging process with sclerosis affecting only the conduction tissue.

DeForest (1956) studied a kindred in which uncomplicated left bundle branch block occurred in 4 persons in 2 generations. Segall (1961) described an instance of father, son, and daughter (of French-Canadian and black intermixture) with right bundle branch block (RBBB) and repeated Stokes-Adams attacks with various atrial arrhythmias and ventricular extrasystoles. The father died at 74 years, 14 years after the first fainting episode. Two asymptomatic brothers showed the electrocardiographic changes of Wolff-Parkinson-White.

Combrink et al. (1962) described a South African family in which the mother had RBBB and died at age 35 years in a Stokes-Adams attack. Of 4 children, 3 had RBBB. The mother's parents had both died suddenly in their 30s. One of her brothers was said to have a cardiac conduction disturbance, another had dextrocardia, while 3 other sibs were apparently normal. Follow-up of this kindred revealed RBBB in 1 of 7 grandchildren (Myburgh et al., 1980). Steenkamp (1972) described a South African family in which 6 of 17 members studied showed disturbance of rhythm or conduction. Brink and Torrington (1977) suggested that the disorder they referred to as progressive familial heart block type I is prevalent in South Africa and is the same disorder as that reported by Combrink et al. (1962) and Steenkamp (1972). Type I heart block in their description tends to have the pattern of a right bundle branch block and/or left anterior hemiblock, manifesting clinically when complete heart block supervenes with syncopal episodes, Stokes-Adams seizures, or sudden death. The risk to life appeared to be greatest at or soon after birth, during puberty and the early twenties, and again toward middle age.

Greenspahn et al. (1976) presented evidence suggesting that a susceptibility to disorder in conduction that is expressed late in life is inherited. Lorber et al. (1988) observed a father and 2 sons with an electrocardiographic pattern of pseudo left posterior hemiblock and incomplete right bundle branch block that resulted in right axis deviation.

Husson et al. (1973) reported a family in which a girl had complete heart block at age 2 years and died at age 10 with ventricular fibrillation. A brother had right bundle branch block at age 15 years and complete heart block at age 17. A sister, aged 17 years, had prolonged intraventricular conduction time with incomplete right bundle branch block. In this family, complete heart block and bundle branch block were expressions of the same genotype.

▼ Molecular Genetics
In a French family with Lenegre-Lev disease, Schott et al. (1999) excluded linkage to the cardiac conduction defect locus on chromosome 19 and to other loci for inherited cardiac diseases associated with conduction defects. Because of the potential role of the sodium current in the infranodal conduction of the cardiac impulse, Schott et al. (1999) analyzed the SCN5A gene and identified a splice site mutation (600163.0009) in affected members of the French family.

In a Dutch family with congenital nonprogressive conduction defect, Schott et al. (1999) identified a deletion in the SCN5A gene (600163.0010). The authors suggested that, depending on the consequences of a mutation on the sodium channel characteristics, the resulting phenotype may be progressive or intermediate.

▼ History
Morquio (1901) and Osler (1903), whose names are known in other connections, are credited with the earliest reports of familial disturbance in cardiac conduction. Although most reports of congenital heart block have concerned affected sibs (most of which may represent cases of congenital complete heart block due to circulating autoantibodies in the mother with lupus), 2 or more generations have been affected often enough to prove dominant inheritance of one or more forms (Fulton et al., 1910; Wallgren and Winblad, 1937; Wendkos and Study, 1947). Similarly, late-onset heart block may be heritable as a dominant; variability in expression is common.

In the family reported by Gazes et al. (1965), conduction disturbances occurred in 3 or 4 generations. In most of the affected persons the heart block was of second degree with episodes of third-degree (complete) atrioventricular dissociation, leading to Adams-Stokes seizures. The family of Wendkos and Study (1947) consisted of a father with the Wolff-Parkinson-White syndrome and 2 offspring with congenital complete heart block. In the family reported by Fulton et al. (1910), 3 to 1 block was thought to be present in the father, complete block in a 22-month-old son, and 2 to 1 block in a 20-year-old daughter. Amatller-Trias et al. (1966) described father (aged 43), son (aged 19) and daughter (aged 22) with first-degree heart block (prolonged PR interval).

Sarachek and Leonard (1972) reviewed 19 reports of familial bradycardia. Ten families had pure AV block, 6 had members with AV block or sinus bradycardia, and 3 had pure sinus bradycardia. Eight families had congenital heart block and 8 had onset in adulthood. Schaal et al. (1973) studied the family of a 69-year-old woman with right bundle branch block and left axis deviation, who later developed complete heart block. Six relatives had heart block and 26 had abnormal electrocardiograms. First-degree heart block is a feature of a form of familial atrial septal defect and has been reported to precede more severe disturbances of AV conduction in cases of familial heart block (Paul et al., 1958).

Gambetta et al. (1973) described a kindred in which 8 persons in 4 generations had prolonged PR interval. There was male-to-male transmission and 2 instances of skipped generation.

Fauchier et al. (1979) described 4 brothers, with a maximal age difference of 20 years, who showed sinoatrial block, supra-hisian atrioventricular block, and paroxysmal atrial arrhythmias. The disorder had progressed to partial atrial standstill in the eldest. Left anterior hemiblock was also present in the 2 youngest brothers. The disorder was well tolerated. The authors referred to the disorder as familial idiopathic binodal block and supported autosomal dominant inheritance. Variable degrees of nonspecific fibrosis of the nodal and atrial tissues were thought to be present. See also cardiac conduction defect (115080).

Barak et al. (1987) described studies of an instructive family ascertained through a fetus found to have second-degree AV block at 35 weeks of gestation. The conduction disturbance was diagnosed by ultrasonography. Seven of the family members were found to have sinus node dysfunction ('sick sinus syndrome') and/or various degrees of atrioventricular block. Three of them were children aged 9 months to 6 years, and all were asymptomatic. The symptomatic family members were 2 adults. One of them had a pacemaker inserted for a complete AV block and Adams-Stokes attacks, while the other had had several fainting attacks.

(文献)
(1) Morquio L: Sur une maladie infantile et familiale caracterisee par des modifications permanentes du pouls, des attaques syncopales et epileptiformes et la mort subite. Arch. Med. Enfants 4: 467-475, 1901
(2) Osler W: On the so-called Stokes-Adams disease. Lancet II: 516-524, 1903
(3) Fulton ZMK et al. Congenital heart block occurring in a father and two children, one an infant. Am. J. Med. Sci. 140: 339-348, 1910
(4) Wallgren A, Winblad S: Congenital heart-block. Acta Paediat. 20: 175-204, 1937
(5) Wendkos MH, Study RS: Familial congenital complete A-V heart blocks. Am. Heart J. 34: 138-142, 1947
(6) Deforest RE: Four cases of 'benign' left bundle branch block in the same family. Am Heart J 51: 398-404, 1956
(7) Paul MH et al. Congenital complete atrioventricular block: problems of clinical assessment. Circulation 18: 183-190, 1958
(8) Segall HN: Congenital arrhythmias and conduction abnormalities in a father and four children. Canad Med Assoc J 84: 1283-1296, 1961
(9) Combrink JM et al. Familial bundle branch block. Am Heart J 64: 397-400, 1962
(10) Lenegre J: The pathology of complete atrio-ventricular block. Prog. Cardiovas. Dis. 6: 317-323, 1964
(11) Gazes PC et al. Congenital familial cardiac conduction defects. Circulation 32: 32-34, 1965
(12) Amatller-Trias A et al. Bloqueo auriculo-ventricular de primer grado de tipo familiar. Med. Clin. 46: 27-34, 1966
(13) Lev M et al. The pathogenesis of atrioventricular block in coronary disease. Circulation 42: 409-425, 1970
(14) Sarachek NS, Leonard JJ: Familial heart block and sinus bradycardia: classification and natural history. Am. J. Cardiol. 29: 451-458, 1972
(15) Steenkamp WFJ: Familial trifascicular block. Am Heart J 84: 758-760, 1972
(16) Williams DO et al. Familial atrial cardiomyopathy with heart block. Quart. J. Med. 41: 491-508, 1972
(17) Gambetta M et al. Sick sinus syndrome in a patient with familial PR prolongation. Chest 64: 520-523, 1973
(18) Husson GS et al. Familial congenital bundle branch system disease. Am. J. Cardiol. 32: 365-369, 1973
(19) Schaal SF et al. Familial right bundle-branch block, left axis deviation, multiple heart block, and early death: a heritable disorder of cardiac conduction. Ann. Intern. Med. 79: 63-66, 1973
(20) Amat-y-Leon F et al. Familial atrial dysrhythmia with A-V block: intracellular microelectrode, clinical electrophysiologic, and morphologic observations. Circulation 50: 1097-1104, 1974
(21) Lynch HT et al. Hereditary progressive atrioventricular conduction defect. Am. J. Cardiol. 36: 297-301, 1975
(22) Greenspahn BR et al. Chronic bifascicular block: evaluation of familial factors. Ann Intern Med 84: 521-525, 1976
(23) Brink AJ, Torrington M. Progressive familial heart block--two types. S Afr Med J 52: 53-59, 1977
(24) Stephan E; Hereditary bundle branch system defect: survey of a family with four affected generations. Am Heart J 95: 89-95, 1978
(25) Fauchier JP et al. Le bloc binodal idiopathique et familial de l'adulte. Arch. Mal. Coeur 72: 1059-1068, 1979
(26) Myburgh DP et al. Familial right bundle branch block. S Afr Med J 58: 393, 1980
(27) Stephan E et al. Familial fascicular block: histologic features of Lev's disease. Am. Heart J. 109: 1399-1401, 1985
(28) van der Merwe P-L et al. Progressive familial heart block. part II. Clinical and ECG confirmation of progression: report on 4 cases. S. Afr. Med. J. 70: 356-357, 1986
(29) Barak M et al. Familial combined sinus node and atrioventricular conduction dysfunctions. Int. J. Cardiol. 15: 231-239, 1987
(30) Lorber A et al. Hereditary right axis deviation: electrocardiographic pattern of pseudo left posterior hemiblock and incomplete right bundle branch block. Int J Cardiol 20: 399-402, 1988
(31) van der Merwe P-L et al. Progressive familial heart block (type I): a follow-up study after 10 years. S. Afr. Med. J. 73: 275-276, 1988
(32) Brink PA et al. Genetic linkage studies of progressive familial heart block, a cardiac conduction disorder. S. Afr. J. Med. Sci. 90: 236-240, 1994
(33) Brink PA et al. Gene for progressive familial heart block type I maps to chromosome 19q13. Circulation 91: 1633-1640, 1995
(34) de Meeus A et al. An isolated cardiac conduction disease maps to chromosome 19q. Circ. Res. 77: 735-740, 1995
(35) Stephan E et al. Hereditary bundle branch defect: right bundle branch blocks of different causes have different morphologic characteristics. Am. Heart J. 133: 249-256, 1997
(36) Schott J-J et al. Cardiac conduction defects associate with mutations in SCN5A. (Letter) Nature Genet. 23: 20-21, 1999

2010/06/10
2011/07/09
2013/01/30
2014/11/13 変異追加
2016/05/24 SNP
2017/01/13 RCV
2019/06/14 ノート改訂