Alternative titles; symbols
SNOMEDCT: 53043001; ORPHA: 154, 300751; DO: 0110425;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q22 | Cardiomyopathy, dilated, 1A | 115200 | Autosomal dominant | 3 | LMNA | 150330 |
A number sign (#) is used with this entry because dilated cardiomyopathy-1A (CMD1A) is caused by heterozygous mutation in the lamin A/C gene (LMNA; 150330) on chromosome 1q22.
Dilated cardiomyopathy (CMD) is characterized by cardiac dilatation and reduced systolic function. CMD is the most frequent form of cardiomyopathy and accounts for more than half of all cardiac transplantations performed in patients between 1 and 10 years of age. A heritable pattern is present in 20 to 30% of cases. Most familial CMD pedigrees show an autosomal dominant pattern of inheritance, usually presenting in the second or third decade of life (summary by Levitas et al., 2010).
Genetic Heterogeneity of Dilated Cardiomyopathy
Mutations in many other genes have been found to cause different forms of autosomal dominant dilated cardiomyopathy. These include CMD1C (601493), with or without left ventricular noncompaction, caused by mutation in the LDB3 gene (605906) on 10q23; CMD1D (601494), caused by mutation in the TNNT2 gene (191045) on 1q32; CMD1E (601154), caused by mutation in the SCN5A gene (600163) on 3p22; CMD1G (604145), caused by mutation in the TTN gene (188840) on 2q31; CMD1I (604765), caused by mutation in the DES gene (125660) on 2q35; CMD1J (605362), caused by mutation in the EYA4 gene (603550) on 6q23; CMD1L (606685), caused by mutation in the SGCD gene (601411) on 5q33; CMD1M (607482), caused by mutation in the CSRP3 gene (600824) on 11p15; CMD1O (608569), caused by mutation in the ABCC9 gene (601439) on 12p12; CMD1P (609909), caused by mutation in the PLN gene (172405) on 6q22; CMD1R (613424), caused by mutation in the ACTC gene (102540) on 15q14; CMD1S (613426), caused by mutation in the MYH7 gene (160760) on 14q12; CMD1U (613694), caused by mutation in the PSEN1 gene (104311) on 14q24; CMD1V (613697), caused by mutation in the PSEN2 gene (600759) on 1q42; CMD1W (611407), caused by mutation in the gene encoding metavinculin (VCL; 193065) on 10q22; CMD1X (611615), caused by mutation in the gene encoding fukutin (FKTN; 607440) on 9q31; CMD1Y (611878), caused by mutation in the TPM1 gene (191010) on 15q22; CMD1Z (611879), caused by mutation in the TNNC1 gene (191040) on 3p21; CMD1AA (612158), caused by mutation in the ACTN2 gene (102573) on 1q43; CMD1BB (612877), caused by mutation in the DSG2 gene (125671) on 18q12; CMD1CC (613122), caused by mutation in the NEXN gene (613121) on 1p31; CMD1DD (613172), caused by mutation in the RBM20 gene (613171) on 10q25; CMD1EE (613252), caused by mutation in the MYH6 gene (160710) on 14q12; CMD1FF (613286), caused by mutation in the TNNI3 gene (191044) on 19q13; CMD1GG (613642), caused by mutation in the SDHA gene (600857) on 5p15; CMD1HH (613881), caused by mutation in the BAG3 gene (603883) on 10q26; CMD1II (615184), caused by mutation in the CRYAB gene (123590) on 6q21; CMD1JJ (615235), caused by mutation in the LAMA4 gene (600133) on 6q21; CMD1KK (615248), caused by mutation in the MYPN gene (608517) on 10q21; CMD1LL (615373), caused by mutation in the PRDM16 gene (605557) on 1p36; CMD1MM (see 615396), caused by mutation in the MYBPC3 gene (600958) on 11p11; CMD1NN (615916), caused by mutation in the RAF1 gene (164760) on 3p25; CMD1OO (620247), caused by mutation in the VEZF1 gene (606747) on chromosome 17q22; and CMD1PP (see 617047), caused by mutation in the FLNC gene (102565) on chromosome 7q32.
Several additional loci for autosomal dominant familial dilated cardiomyopathy have been mapped: CMD1B (600884) on 9q13; CMD1H (604288) on 2q14-q22; CMD1K (605582) on 6q12-q16; and CMD1Q (609915) on 7q22.3-q31.1.
Autosomal recessive CMD includes CMD2A (611880), caused by mutation in the TNNI3 gene (191044) on 19q13; CMD2B (614672), caused by mutation in the GATAD1 gene (614518) on 7q21; CMD2C (618189), caused by mutation in the PPCS gene (609853) on 1p34; CMD2D (619371), caused by mutation in the RPL3L gene (617416) on 16p13; CMD2E (619492), caused by mutation in the JPH2 gene (605267) on chromosome 20q13; CMD2F (619747), caused by mutation in the BAG5 gene (603885) on chromosome 14q32; CMD2G (619897), caused by mutation in the LMOD2 gene (608006) on chromosome 7q31; CMD2H (620203), caused by mutation in the GET3 gene (601913) on chromosome 19p13; CMD2I (620462), caused by mutation in the CAP2 gene (618385) on chromosome 6p22; and CMD2J (620635), caused by mutation in the FLII gene (600362) on chromosome 17p11.
An X-linked form of CMD (CMD3B; 302045) is caused by mutation in the DMD gene (300377). An X-linked form previously designated CMD3A was found to be the same as Barth syndrome (302060).
Reclassified CMD Symbols
The symbol CMD1F was formerly used for a disorder later found to be the same as desmin-related myopathy (601419).
The symbol CMD1N (see 607487) was previously used for a form of dilated cardiomyopathy reported to be caused by a mutation in the TCAP gene (604488.0003); this variant has been reclassified as a variant of unknown significance.
The symbol CMD1T was previously used for a form of dilated cardiomyopathy reported to be caused by a mutation in the TMPO gene (188380.0001); this variant has been reclassified as a variant of unknown significance.
Dilated cardiomyopathy, a disorder characterized by cardiac dilation and reduced systolic function, represents an outcome of a heterogeneous group of inherited and acquired disorders. Olson and Keating (1996) noted that causes include myocarditis, coronary artery disease, systemic diseases, and myocardial toxins; idiopathic dilated cardiomyopathy in which these causes are excluded represents approximately one-half of all cases. Idiopathic dilated cardiomyopathy occurs with a prevalence of about 36.5 per 100,000; it accounts for more than 10,000 deaths in the U.S. annually and is the primary indication for cardiac transplantation. Among cases of idiopathic dilated cardiomyopathy, familial occurrence accounts for 20 to 25%, with the exception of rare cases resulting from mutations in dystrophin (e.g., 300377.0021). Familial dilated cardiomyopathy is characterized by an autosomal dominant pattern of inheritance with age-related penetrance. It presents with development of ventricular dilatation and systolic dysfunction usually in the second or third decade of life.
Whitfield (1961) described a family in which 10 members were suffering or had died from cardiomyopathy and 6 others were probably affected. Although both males and females were affected, transmission seemingly occurred only through the female. Schrader et al. (1961) described 2 sisters with familial idiopathic cardiomegaly. Almost certainly the mother, who died at age 34, and probably 1 brother, who died at age 16, had the same condition. In the family reported by Battersby and Glenner (1961), affected persons were limited to 1 sibship and deposits of a nonmetachromatic, diastase-resistant, PAS-positive polysaccharide were described in the myocardium. Undoubtedly heterogeneity exists in the group of cardiomyopathies. Boyd et al. (1965) suggested that there may be 3 forms: (1) a form with predominant fibrosis, (2) a form with predominant hypertrophy (see ventricular hypertrophy, hereditary; 192600), and (3) a form with deposits described above. See amyloidosis III (176300.0007) for another familial cardiomyopathy. Kariv et al. (1966) observed 6 affected persons in 3 generations. In 2 of these persons, Adams-Stokes attacks required an artificial pacemaker. The affected males showed significant increase in the serum levels of multiple muscle-derived enzymes. Heterogeneity was suggested by the finding of normal serum enzyme levels in affected members of a second family. Rywlin et al. (1969) favored the view that obstructive and nonobstructive forms of familial cardiopathy are different expressions of a single entity. Classification into 'hypertrophic' and 'congestive' clinical types by Goodwin (1970) implies the same. Sommer et al. (1972) took an opposite view, i.e., that there is a separate nonobstructive familial cardiomyopathy. They described an Amish family with affected persons in 3 generations. Severity varied widely. The most severely affected pursued a rapidly fatal course whereas others manifested mainly conduction defects compatible with long survival. Machida et al. (1971) described a Japanese family with affected persons in 2 and perhaps 3 generations with male-to-male transmission. Emanuel et al. (1971) suggested that both dominant and recessive forms may exist. The possibility of an autosomal recessive form of congestive cardiomyopathy was raised by Yamaguchi et al. (1977), who found an astoundingly high rate of parental consanguinity (about 64%) and a segregation ratio of 0.196 consistent with autosomal recessive inheritance.
Moller et al. (1979) described an autosomal dominant form of congestive cardiomyopathy. The earliest sign of the disease was arrhythmia and/or conduction defects. Symptoms of pump failure had their onset in adulthood. Three members of the extensively affected kindred had died suddenly. Septal hypertrophy was found in 2 affected persons.
Fragola et al. (1988) studied 44 first-degree relatives of 12 probands with idiopathic dilated cardiomyopathy. Affected relatives were identified in 4 of 12 families. In each case, the affected relatives were sibs. This may be due to a late age of onset for expression of genetic factors involved in the etiology of this condition.
O'Connell et al. (1984) used endomyocardial biopsy and gallium-67 scans in patients with dilated cardiomyopathy to demonstrate a subset of patients with myocardial inflammation. Histologic confirmation was found at autopsy. A defect in suppressor lymphocyte function was found in 1 patient, who showed improvement with immunosuppressive therapy. In 1 family, 5 persons in 3 generations were affected; in another, a father and 2 brothers were affected. Battersby and Glenner (1961) reported striking pericardial effusion in a family with cardiomyopathy. Other early reports (e.g., Evans, 1949) have commented on inflammatory changes found at necropsy. Pericardial effusion occurs episodically with the iron-overload cardiomyopathy of multitransfused thalassemia and occurs also in the cardiomyopathy of Friedreich ataxia (229300).
Ozick et al. (1984) reported identical twin sisters with congestive cardiomyopathy and autoimmune thyroid disease. Both had antithyroid microsomal antibodies and cytolytic antiheart myolemmal antibodies. The postpartum state may have been a factor in one of the twins; both cardiomyopathy and autoimmune thyroid disease may become clinically apparent in the postpartum period. Gardner et al. (1985) evaluated a kindred in which 12 persons had cardiomegaly with poor ventricular function and/or dysrhythmia. The disorder was evident by echocardiogram in a 6-month-old infant. Skeletal muscle biopsies showed subtle myopathic alterations. The pedigree, spanning 5 generations, was consistent with autosomal dominant inheritance. Gardner et al. (1987) described a family in which multiple members in 3 and probably 4 generations had dilated cardiomyopathy with overt clinical onset between the fourth and seventh decades. Dysrhythmia was frequent. They concluded that there might be an associated skeletal myopathy manifested by very mild proximal weakness or detectable only on biopsy. MacLennan et al. (1987) described 8 affected individuals, 4 of whom were males in 3 generations. Average age at presentation was 39.5 years. Average time to death from onset of symptoms suggestive of cardiomyopathy in 6 affected members was 16 months. One member died suddenly after being asymptomatic. The myocardium showed variation in muscle fiber size and interstitial fibrosis.
Graber et al. (1986) described a large kindred with an autosomal dominant form of disease of the cardiac conduction system and of the myocardium. Stage I occurred in the second and third decades and was characterized by absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II was marked by first-degree AV block in the third and fourth decades. Stage III occurred in the fourth and fifth decades and was accompanied by chest pain, fatigue, lightheadedness, and advanced AV block, followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, was characterized by congestive heart failure and recurrent ventricular arrhythmias. Right ventricular endomyocardial biopsy specimens showed progressive changes. At autopsy in the proband, the atrial changes were more severe than the ventricular ones. This suggested that the disorder discussed in entry 108770 is the same as this condition. While there was a range in the phenotypic expression of the inherited gene defect in this kindred, the dilated cardiomyopathy was less impressive than the dysrhythmia. Arrhythmias were the earliest manifestation of the disease (in the second to third decade).
Schmidt et al. (1988) studied familial dilated cardiomyopathy in 6 families. The familial nature of the disorder was not readily apparent in 3 of these families until thorough family investigations were performed. The authors suggested that the family history should be reviewed in all patients with dilated cardiomyopathy and that further investigation of relatives should be performed if there are cases of unexplained heart disease, sudden unexpected death, or syncopal episodes. Echocardiography is a convenient noninvasive tool for these investigations. Early diagnosis is indicated for 2 reasons: treatment of significant arrhythmias may prevent sudden unexpected death, and genetic counseling can be provided. In studies of the first-degree relatives of 59 index cases with idiopathic dilated cardiomyopathy, Michels et al. (1992) found that 18 relatives from 12 families had dilated cardiomyopathy. Thus, 12 of the 59 index patients (20.3%) had familial disease. No differences in age, sex, severity of disease, exposure to selected environmental factors, or electrocardiographic or echocardiographic features were detected between the index patients with familial disease and those with nonfamilial disease. A noteworthy finding was that 22 of 240 healthy relatives (9.2%) with normal ejection fractions had increased left ventricular diameters during systole or diastole (or both), as compared with 2 of 112 healthy control subjects (1.8%) who were studied separately. In a case-control study of idiopathic dilated cardiomyopathy in Baltimore, a roughly 3-fold increase in risk was observed among blacks after adjustment for potential confounding variables (Coughlin et al., 1990). The increased frequency of dilated cardiomyopathy in black males was the basis in the past of the designation 'Osler-2 myocarditis'; Osler-2 was the black male ward at The Johns Hopkins Hospital.
Michels et al. (1993) performed PCR-based assays and Southern blot analysis of the dystrophin gene (DMD; 300377) in 27 males with idiopathic dilated cardiomyopathy. Five families had familial disease, without male-to-male transmission in 4 families. In the fifth family, there was no evidence of male-to-male transmission when the family was entered into the study, but on follow-up the index patient's son was found to have developed the disease. None of the patients had clinical evidence of skeletal muscle disease or any systemic illness that could cause heart disease. The mean age of the patients was 50.2 years; the range of age was 5 to 72 years. No dystrophin gene defects were found.
Csanady et al. (1995) compared 31 familial and 209 nonfamilial cases of dilated cardiomyopathy. They concluded that the familial form is more malignant: it occurs at an earlier age and progresses more rapidly than the nonfamilial form.
For a review of the genetic and clinical heterogeneity of familial dilated cardiomyopathy, see Seidman and Seidman (2001).
Meune et al. (2006) investigated the efficacy of implantable cardioverter-defibrillators (ICDs) in the primary prevention of sudden death in patients with cardiomyopathy due to lamin A/C gene mutations. Patients referred for permanent cardiac pacing were systematically offered the implantation of an ICD. The patients were enrolled solely on the basis of the presence of lamin A/C mutations associated with cardiac conduction defects. Indications for pacemaker implantation were progressive conduction block and sinus block. In all, 19 patients were treated. Meune et al. (2006) concluded that ICD implantation in patients with lamin A/C mutations who are in need of a pacemaker is effective in treating possibly lethal tachyarrhythmias, and that implantation of an ICD, rather than a pacemaker, should be considered for such patients.
Lee et al. (2019) modeled LMNA-related dilated cardiomyopathy (CMD) in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). These cardiomyocytes were developed from a large family cohort, members of which carried a frameshift mutation in LMNA that led to early termination of translation. Three of the carriers presented with atrial fibrillation that progressed to atrioventricular block, ventricular tachycardia, and CMD. Electrophysiologic studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis that led to arrhythmias at the single-cell level. Mechanistically, Lee et al. (2019) showed that the platelet-derived growth factor (PDGF) signaling pathway is activated in mutant iPSC-CMs compared to isogenic control iPSC-CMs. Conversely, pharmacologic and molecular inhibition of the PDGF signaling pathway ameliorated the arrhythmic phenotypes of mutant iPSC-CMs in vitro. The findings of Lee et al. (2019) suggested that the activation of the PDGF pathway contributes to the pathogenesis of LMNA-related DCM, and that PDGFRB (173410) is a potential therapeutic target.
Koike et al. (1987) described 2 families with dilated cardiomyopathy. In 1 of these families, the mode of inheritance was autosomal dominant; in the other, it appeared to be autosomal recessive. In both families, the pattern of inheritance was consistent with linkage to the HLA locus; however, because the families were small, the lod scores were low. From linkage studies in 12 families, Olson et al. (1995) excluded genetic linkage between the disease phenotype and a 21-cM region spanning the HLA cluster in at least 60% of the families.
By linkage studies, Kass et al. (1994) demonstrated linkage of the disease locus to polymorphic loci near the centromere of chromosome 1; maximum multipoint lod score = 13.2 in the interval between D1S305 and D1S176. Based on the disease phenotype and the map location, Kass et al. (1994) speculated that the gap junction protein connexin-40 (121013) is a candidate for the site of mutations that result in conduction system disease and dilated cardiomyopathy.
Csanady et al. (1995) compared 31 familial and 209 nonfamilial cases of dilated cardiomyopathy. They concluded that the familial form is more malignant: it occurs at an earlier age and progresses more rapidly than the nonfamilial form.
Among 100 patients with dilated cardiomyopathy, McKenna et al. (1997) found that familial prevalence was definite in 14 of 56 (25%) and possible in 25 of 56 (45%). The HLA-DR4 frequency in the 100 patients with dilated cardiomyopathy was similar to that in 9,000 controls; however, the DR4 subtype was significantly more common in the 25 probands with a familial tendency to dilated cardiomyopathy than in the 31 probands with nonfamilial dilated cardiomyopathy. McKenna et al. (1997) concluded that there is an HLA-linked predisposition to familial dilated cardiomyopathy.
The transmission pattern of dilated cardiomyopathy-1A in the families reported by Fatkin et al. (1999) was consistent with autosomal dominant inheritance.
In 5 of 11 families with autosomal dominant dilated cardiomyopathy and conduction system defects, Fatkin et al. (1999) identified 5 heterozygous missense mutations in the LMNA gene (150330.0005-150330.0009). Each mutation caused heritable, progressive conduction system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Furthermore, serum creatine kinase levels were normal in family members with mutations in the lamin rod domain, but mildly elevated in some family members with a defect in the tail domain of lamin C. The findings indicated that the lamin A/C intermediate filament protein plays an important role in cardiac conduction and contractility. In an editorial accompanying the report of Fatkin et al. (1999), Graham and Owens (1999) tabulated the chromosomal locations of the known loci responsible for inherited forms of dilated cardiomyopathy.
Brodsky et al. (2000) presented a large family with a severe autosomal dominant dilated cardiomyopathy with an atrioventricular conduction defect in some affected members. In addition, some affected individuals had skeletal muscle symptoms varying from minimal weakness to a mild limb-girdle muscular dystrophy. One individual had a pattern of skeletal muscle involvement that the authors considered consistent with mild Emery-Dreifuss muscular dystrophy. Affected individuals were heterozygous for a single nucleotide deletion in the lamin A/C gene (150330.0013). The authors highlighted the wide range in phenotype arising from this mutation.
In 2 families with dilated cardiomyopathy with conduction defects, Sebillon et al. (2003) identified 2 different mutations in the LMNA gene (150330.0028, 150330.0029). In 1 family, the phenotype was characterized by early-onset atrial fibrillation preceding or coexisting with dilated cardiomyopathy.
Taylor et al. (2003) screened the LMNA gene in 40 families with familial CMD and 9 patients with sporadic CMD and identified mutations in 3 families (see, e.g., 150330.0017) and 1 sporadic patient (S573L; 150330.0041). There was significant phenotypic variability in the patients studied, but the presence of skeletal muscle involvement, supraventricular arrhythmia, conduction defects, and 'mildly' dilated cardiomyopathy were predictors of LMNA mutations. The LMNA mutation carriers had a significantly poorer cumulative survival compared with noncarrier CMD patients, with an event-free survival at age 45 years of 31% versus 75%, respectively.
In affected members of a French family with dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias and skeletal muscular dystrophy of the quadriceps muscles, Charniot et al. (2003) identified an arg377-to-his mutation in the LMNA gene (R377H; 150330.0017). The same mutation had been reported in patients with limb-girdle muscular dystrophy type-1B (see EDMD2, 181350), a slowly progressive muscular dystrophy with age-related atrioventricular cardiac conduction disturbances and the absence of early contractures. Charniot et al. (2003) suggested that factors other than the R377H mutation may have influenced the phenotypic expression in this family.
Kimura (2011) reviewed the contribution of genetics in the pathogenesis of dilated cardiomyopathy and discussed functional aspects of sarcolemmal, contractile element, Z disc element, sarcoplasmic element, and nuclear lamina mutations. The author noted that there was no major disease gene for Japanese CMD patients reported to date.
Associations Pending Confirmation
Mutation in the ILK gene (see 602366.0001) is a possible cause of CMD, as is mutation in the ITGB1BP2 gene (see 300332.0001).
For discussion of a possible association between variation in the SOD2 gene (147460) and nonfamilial dilated cardiomyopathy or lethal neonatal dilated cardiomyopathy, see 147460.0001 and 147460.0002, respectively.
For discussion of a possible association between dilated cardiomyopathy and variation in the MYBPHL gene, see 619807.0001.
Gupta et al. (2010) analyzed the LMNA gene in heart samples from 25 unrelated CMD patients and identified 3 heterozygous missense mutations in 3 patients as well as a heterozygous deletion of exons 3 to 12 in 1 patient. The LMNA deletion and 1 of the missense mutations were associated with major cardiomyocyte nuclear envelope abnormalities, whereas the other 2 missense mutations were found in patients without specific nuclear envelope abnormalities. Gupta et al. (2010) stated that they did not find any evidence of a genotype/phenotype relationship between the onset and severity of CMD, the presence of nuclear abnormalities, and the presence or absence of LMNA mutations.
Elliott et al. (2003) generated HLA-DQ8 transgenic AI-beta knockout NOD mice that did not show insulitis or diabetes but developed dilated cardiomyopathy. The constellation of findings of spontaneously arising destructive focal lymphocytic infiltrates within the myocardium, rising titers of circulating anticardiac autoantibodies, dilation of the cardiac chambers, and gradual progression to end-stage heart failure bore a striking resemblance to clinical features in humans with idiopathic dilated cardiomyopathy. Elliott et al. (2003) concluded that this transgenic strain provides a highly relevant animal model for human autoimmune myocarditis and postinflammatory dilated cardiomyopathy.
Mounkes et al. (2005) generated mice expressing the human N195K (150330.0007) mutation and observed characteristics consistent with CMD1A. Continuous electrocardiographic monitoring of cardiac activity demonstrated that N195K-homozygous mice died at an early age due to arrhythmia. Immunofluorescence and Western blot analysis showed that Hf1b/Sp4 (600540), connexin-40 (GJA5; 121013), and connexin-43 (GJA1; 121014) were misexpressed and/or mislocalized in N195K-homozygous mouse hearts. Desmin staining revealed a loss of organization at sarcomeres and intercalated disks. Mounkes et al. (2005) hypothesized that mutations within the LMNA gene may cause cardiomyopathy by disrupting the internal organization of the cardiomyocyte and/or altering the expression of transcription factors essential to normal cardiac development, aging, or function.
Barry, M., Hall, M. Familial cardiomyopathy. Brit. Heart J. 24: 613-624, 1962. [PubMed: 13969597] [Full Text: https://doi.org/10.1136/hrt.24.5.613]
Battersby, E. J., Glenner, G. G. Familial cardiomyopathy. Am. J. Med. 30: 382-391, 1961. [PubMed: 13687796] [Full Text: https://doi.org/10.1016/0002-9343(61)90048-1]
Biorck, G., Orinius, E. Familial cardiomyopathies. Acta Med. Scand. 176: 407-424, 1964. [PubMed: 14221653]
Bishop, J. M., Campbell, M., Jones, E. W. Cardiomyopathy in four members of a family. Brit. Heart J. 24: 715-728, 1962. [PubMed: 13971225] [Full Text: https://doi.org/10.1136/hrt.24.6.715]
Boyd, D. L., Mishkin, M. E., Feigenbaum, H., Genovese, P. D. Three families with familial cardiomyopathy. Ann. Intern. Med. 63: 386-401, 1965. [PubMed: 14327505] [Full Text: https://doi.org/10.7326/0003-4819-63-3-386]
Brodsky, G. L., Muntoni, F., Miocic, S., Sinagra, G., Sewry, C., Mestroni, L. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation 101: 473-476, 2000. [PubMed: 10662742] [Full Text: https://doi.org/10.1161/01.cir.101.5.473]
Charniot, J.-C., Pascal, C., Bouchier, C., Sebillon, P., Salama, J., Duboscq-Bidot, L., Peuchmaurd, M., Desnos, M., Artigou, J.-Y., Komajda, M. Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype. Hum. Mutat. 21: 473-481, 2003. [PubMed: 12673789] [Full Text: https://doi.org/10.1002/humu.10170]
Coughlin, S. S., Szklo, M., Baughman, K., Pearson, T. A. The epidemiology of idiopathic dilated cardiomyopathy in a biracial community. Am. J. Epidemiol. 131: 48-56, 1990. [PubMed: 2293752] [Full Text: https://doi.org/10.1093/oxfordjournals.aje.a115484]
Csanady, M., Hogye, M., Kallai, A., Forster, T., Szarazajtai, T. Familial dilated cardiomyopathy: a worse prognosis compared with sporadic forms. Brit. Heart J. 74: 171-173, 1995. [PubMed: 7546997] [Full Text: https://doi.org/10.1136/hrt.74.2.171]
Elliott, J. F., Liu, J., Yuan, Z.-N., Bautista-Lopez, N., Wallbank, S. L., Suzuki, K., Rayner, D., Nation, P., Robertson, M. A., Liu, G., Kavanagh, K. M. Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IA-beta knockout NOD mice. Proc. Nat. Acad. Sci. 100: 13447-13452, 2003. [PubMed: 14570980] [Full Text: https://doi.org/10.1073/pnas.2235552100]
Emanuel, R., Withers, R., O'Brien, K. Dominant and recessive modes of inheritance in idiopathic cardiomyopathy. Lancet 298: 1065-1067, 1971. Note: Originally Volume II. [PubMed: 4106916] [Full Text: https://doi.org/10.1016/s0140-6736(71)90383-7]
Evans, W. Familial cardiomegaly. Brit. Heart J. 11: 68-82, 1949. [PubMed: 18113470] [Full Text: https://doi.org/10.1136/hrt.11.1.68]
Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr., Spudich, S., De Girolami, U., Seidman, J. G., Seidman, C. E. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. New Eng. J. Med. 341: 1715-1724, 1999. [PubMed: 10580070] [Full Text: https://doi.org/10.1056/NEJM199912023412302]
Fragola, P. V., Autore, C., Picelli, A., Sommariva, L., Cannata, D., Sangiorgi, M. Familial idiopathic dilated cardiomyopathy. Am. Heart J. 115: 912-914, 1988. [PubMed: 3354422] [Full Text: https://doi.org/10.1016/0002-8703(88)90900-3]
Gardner, R. J. M., Ardinger, H. H., Florentine, M. S., Hanson, J. W., Hart, M. N., Hinrichs, R. L., Ionasescu, V. V., Mahoney, L. T., Rose, E. E., Skorton, D. J. Dominantly inherited dilated cardiomyopathy with skeletal myopathy. (Abstract) Am. J. Hum. Genet. 37: A54, 1985.
Gardner, R. J. M., Hanson, J. W., Ionasescu, V. V., Ardinger, H. H., Skorton, D. J., Mahoney, L. T., Hart, M. N., Rose, E. F., Smith, W. L., Florentine, M. S., Hinrichs, R. L. Dominantly inherited dilated cardiomyopathy. Am. J. Med. Genet. 27: 61-73, 1987. [PubMed: 3605207] [Full Text: https://doi.org/10.1002/ajmg.1320270108]
Goodwin, J. F. Congestive and hypertrophic cardiomyopathies. Lancet 295: 732-739, 1970. Note: Originally Volume I. [PubMed: 4191245]
Graber, H. L., Unverferth, D. V., Baker, P. B., Ryan, J. M., Baba, N., Wooley, C. F. Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected. Circulation 74: 21-35, 1986. [PubMed: 3708775] [Full Text: https://doi.org/10.1161/01.cir.74.1.21]
Graham, R. M., Owens, W. A. Pathogenesis of inherited forms of dilated cardiomyopathy. (Editorial) New Eng. J. Med. 341: 1759-1762, 1999. [PubMed: 10580077] [Full Text: https://doi.org/10.1056/NEJM199912023412309]
Gupta, P., Bilinska, Z. T., Sylvius, N., Boudreau, E., Veinot, J. P., Labib, S., Bolongo, P. M., Hamza, A., Jackson, T., Ploski, R., Walski, M., Grzybowski, J., Walczak, E., Religa, G., Fidzianska, A., Tesson, F. Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption. Basic Res. Cardiol. 105: 365-377, 2010. [PubMed: 20127487] [Full Text: https://doi.org/10.1007/s00395-010-0085-4]
Kariv, I., Szeinberg, A., Fabian, I., Sherf, L., Kreisler, B., Zeltzer, M. A family with cardiomyopathy. Am. J. Med. 40: 140-148, 1966. [PubMed: 5900684] [Full Text: https://doi.org/10.1016/0002-9343(66)90195-1]
Kass, S., MacRae, C., Graber, H. L., Sparks, E. A., McNamara, D., Boudoulas, H., Basson, C. T., Baker, P. B., III, Cody, R. J., Fishman, M. C., Cox, N., Kong, A., Wooley, C. F., Seidman, J. G., Seidman, C. E. A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1-1q1. Nature Genet. 7: 546-551, 1994. [PubMed: 7951328] [Full Text: https://doi.org/10.1038/ng0894-546]
Kimura, A. Contribution of genetic factors to the pathogenesis of dilated cardiopathy--the cause of dilated cardiomyopathy: acquired or genetic? (Genetic-side). Circ. J. 75: 1756-1765, 2011. [PubMed: 21617319] [Full Text: https://doi.org/10.1253/circj.cj-11-0368]
Koike, S., Kawa, S., Yabu, K., Endo, R., Sasaki, Y., Furuta, S., Ota, M. Familial dilated cardiomyopathy and human leucocyte antigen: a report of two family cases. Jpn. Heart J. 28: 941-945, 1987. [PubMed: 3444043] [Full Text: https://doi.org/10.1536/ihj.28.941]
Lee, J., Termglinchan, V., Diecke, S., Itzhaki, I., Lam, C. K., Garg, P., Lau, E., Greenhaw, M., Seeger, T., Wu, H., Zhang, J. Z., Chen, X., and 12 others. Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy. Nature 572: 335-340, 2019. [PubMed: 31316208] [Full Text: https://doi.org/10.1038/s41586-019-1406-x]
Levitas, A., Muhammad, E., Harel, G., Saada, A., Caspi, V. C., Manor, E., Beck, J. C., Sheffield, V., Parvari, R. Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Europ. J. Hum. Genet. 18: 1160-1165, 2010. [PubMed: 20551992] [Full Text: https://doi.org/10.1038/ejhg.2010.83]
Machida, K., Iguchi, K., Yoshimi, S., Saito, Y., Sugishita, Y., Murayama, M., Mori, M., Yamaguchi, H., Ito, I., Uede, H. Familial cardiomyopathy: immunological studies and review of literatures on autopsied cases in Japan. Jpn. Heart J. 12: 40-49, 1971. [PubMed: 5313423]
MacLennan, B. A., Tsoi, E. Y., Maguire, C., Adgey, A. A. J. Familial idiopathic congestive cardiomyopathy in three generations: a family study with eight affected members. Quart. J. Med. 63: 335-347, 1987. [PubMed: 3685246]
McKenna, C. J., Codd, M. B., McCann, H. A., Sugrue, D. D. Idiopathic dilated cardiomyopathy: familial prevalence and HLA distribution. Heart 77: 549-552, 1997. [PubMed: 9227300] [Full Text: https://doi.org/10.1136/hrt.77.6.549]
Meune, C., Van Berlo, J. H., Anselme, F., Bonne, G., Pinto, Y. M., Duboc, D. Primary prevention of sudden death in patients with lamin A/C gene mutations. (Letter) New Eng. J. Med. 354: 209-210, 2006. [PubMed: 16407522] [Full Text: https://doi.org/10.1056/NEJMc052632]
Michels, V. V., Moll, P. P., Miller, F. A., Tajik, A. J., Chu, J. S., Driscoll, D. J., Burnett, J. C., Rodeheffer, R. J., Chesebro, J. H., Tazelaar, H. D. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. New Eng. J. Med. 326: 77-82, 1992. [PubMed: 1727235] [Full Text: https://doi.org/10.1056/NEJM199201093260201]
Michels, V. V., Moll, P. P., Miller, F. A., Tajik, A. J., Driscoll, D. J., Chu, J. S., Burnett, J. C., Chesebro, J. H., Rodeheffer, R. J. Frequency of familial dilated cardiomyopathy in an unselected series of patients with idiopathic dilated cardiomyopathy. (Abstract) Am. J. Hum. Genet. 45 (suppl.): A55, 1989.
Michels, V. V., Pastores, G. M., Moll, P. P., Driscoll, D. J., Miller, F. A., Burnett, J. C., Rodeheffer, R. J., Tajik, J. A., Beggs, A. H., Kunkel, L. M., Thibodeau, S. N. Dystrophin analysis in idiopathic dilated cardiomyopathy. J. Med. Genet. 30: 955-957, 1993. [PubMed: 8301653] [Full Text: https://doi.org/10.1136/jmg.30.11.955]
Moller, P., Lunde, P., Hovig, T., Nitter-Hauge, S. Familial cardiomyopathy: autosomally, dominantly inherited congestive cardiomyopathy with two cases of septal hypertrophy in one family. Clin. Genet. 16: 233-243, 1979. [PubMed: 519893] [Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb00995.x]
Mounkes, L. C., Kozlov, S. V., Rottman, J. N., Stewart, C. L. Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice. Hum. Molec. Genet. 14: 2167-2180, 2005. [PubMed: 15972724] [Full Text: https://doi.org/10.1093/hmg/ddi221]
O'Connell, J. B., Fowles, R. E., Robinson, J. A., Subramanian, R., Henkin, R. E., Gunnar, R. M. Clinical and pathologic findings of myocarditis in two families with dilated cardiomyopathy. Am. Heart J. 107: 127-135, 1984. [PubMed: 6691219] [Full Text: https://doi.org/10.1016/0002-8703(84)90146-7]
Olson, T. M., Keating, M. T. Mapping a cardiomyopathy locus to chromosome 3p22-p25. J. Clin. Invest. 97: 528-532, 1996. [PubMed: 8567977] [Full Text: https://doi.org/10.1172/JCI118445]
Olson, T. M., Thibodeau, S. N., Lundquist, P. A., Schaid, D. J., Michels, V. V. Exclusion of a primary defect at the HLA locus in familial idiopathic dilated cardiomyopathy. J. Med. Genet. 32: 876-880, 1995. [PubMed: 8592331] [Full Text: https://doi.org/10.1136/jmg.32.11.876]
Ozick, H., Hollander, G., Greengart, A., Shani, J., Lichstein, E. Dilated cardiomyopathy in identical twins. Chest 86: 878-880, 1984. [PubMed: 6541991] [Full Text: https://doi.org/10.1378/chest.86.6.878]
Rywlin, A. M., Barold, S. S., Linhart, J. W., Kramer, H. C., Meitus, M. L., Samet, P. Idiopathic familial cardiopathy: a study of two families. J. Genet. Hum. 17: 453-470, 1969. [PubMed: 5387421]
Schmidt, M. A., Michels, V. V., Edwards, W. D., Miller, F. A. Familial dilated cardiomyopathy. Am. J. Med. Genet. 31: 135-143, 1988. [PubMed: 3223495] [Full Text: https://doi.org/10.1002/ajmg.1320310116]
Schrader, W. H., Pankey, G. A., Davis, R. B., Theologides, A. Familial idiopathic cardiomegaly. Circulation 24: 599-606, 1961. [PubMed: 13748557] [Full Text: https://doi.org/10.1161/01.cir.24.3.599]
Sebillon, P., Bouchier, C., Bidot, L. D., Bonne, G., Ahamed, K., Charron, P., Drouin-Garraud, V., Millaire, A., Desrumeaux, G., Benaiche, A., Charniot, J.-C., Schwartz, K., Villard, E., Komajda, M. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations. J. Med. Genet. 40: 560-567, 2003. [PubMed: 12920062] [Full Text: https://doi.org/10.1136/jmg.40.8.560]
Seidman, J. G., Seidman, C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104: 557-567, 2001. [PubMed: 11239412] [Full Text: https://doi.org/10.1016/s0092-8674(01)00242-2]
Sommer, A., Sanz, G., Craenen, J. M., Newton, W. A., Jr. Familial cardiomyopathy. Birth Defects Orig. Art. Ser. VIII(5): 178-181, 1972.
Taylor, M. R. G., Fain, P. R., Sinagra, G., Robinson, M. L., Robertson, A. D., Carniel, E., Di Lenarda, A., Bohlmeyer, T. J., Ferguson, D. A., Brodsky, G. L., Boucek, M. M., Lascor, J., Moss, A. C., Li, W.-L. P., Stetler, G. L., Muntoni, F., Bristow, M. R., Mestroni, L., Familial Dilated Cardiomyopathy Registry Research Group. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J. Am. Coll. Cardiol. 41: 771-780, 2003. Note: Erratum: J. Am. Coll. Cardiol. 42: 590 only, 2003. [PubMed: 12628721] [Full Text: https://doi.org/10.1016/s0735-1097(02)02954-6]
Whitfield, A. G. W. Familial cardiomyopathy. Quart. J. Med. 30: 119-134, 1961. [PubMed: 13784900]
Yamaguchi, M., Toshima, H., Yanase, T., Ikeda, H., Koga, Y., Yoshioka, H., Ito, M., Fujino, T., Yasuda, H. A family study of idiopathic cardiomyopathy. Proc. Jpn. Acad. 53 (ser. B): 209-214, 1977.