Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: overview of 10 years' experience.
OBJECTIVE
With more than 40 dilated cardiomyopathy (DCM)-related genes known, genetic analysis of patients with idiopathic DCM is costly and time-consuming. We describe the yield from genetic analysis in DCM patients in a large Dutch cohort.


RESULTS
We collected cardiological and neurological evaluations, family screenings, and genetic analyses for 418 index patients with idiopathic DCM. We identified 35 (putative) pathogenic mutations in 82 index patients (20%). The type of DCM influenced the yield, with mutations found in 25% of familial DCM cases, compared with 8% of sporadic DCM cases and 62% of cases where DCM was accompanied by neuromuscular disease. A PLN founder mutation (43 cases) and LMNA mutations (19 cases, 16 different mutations) were most prevalent and often demonstrated a specific phenotype. Other mutations were found in: MYH7, DES, TNNT2, DMD, TPM1, DMPK, SCN5A, SGCB (homozygous), and TNNI3. After a median follow-up of 40 months, the combined outcome of death from any cause, heart transplantation, or malignant ventricular arrhythmias in patients with a mutation was worse than in those without an identified mutation (hazard ratio 2.0, 95% confidence interval 1.4-3.0). This seems to be mainly attributable to a high prevalence of malignant ventricular arrhythmias and end-stage heart failure in LMNA and PLN mutation carriers.


CONCLUSIONS
The yield of identified mutations in DCM index patients with clinical clues, such as associated neuromuscular disease or familial occurrence, is higher compared with those without these clues. For sporadic DCM, specific clinical characteristics may be used to select cases for DNA analysis.
Department of Genetics, University of Groningen, University Medical Centre Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. k.y.spaendonck@umcg.nl
Karin Y
KY
van Spaendonck-Zwarts
Ingrid A W
IA
van Rijsingen
Maarten P
MP
van den Berg
Ronald H
RH
Lekanne Deprez
Jan G
JG
Post
Anneke M
AM
van Mil
Folkert W
FW
Asselbergs
Imke
I
Christiaans
Irene M
IM
van Langen
Arthur A M
AA
Wilde
Rudolf A
RA
de Boer
Jan D H
JD
Jongbloed
Yigal M
YM
Pinto
J Peter
JP
van Tintelen
D000328:Adult; D002135:Calcium-Binding Proteins / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009468:Neuromuscular Diseases / Q000150:complications / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D034904:Lamin Type A; D000099211:Phospholamban; C494847:LMNA protein, human
Dilated cardiomyopathy; Genetic analysis; Genetics; Heart failure