TY - JOUR
T1 - Rare variant mutations identified in pediatric patients with dilated cardiomyopathy
AU - Rampersaud, Evadnie
AU - Siegfried, Jill D.
AU - Norton, Nadine
AU - Li, Duanxiang
AU - Martin, Eden
AU - Hershberger, Ray E.
N1 - Funding Information:
Source of funding: this work was supported by National Institutes of Health award R01-HL58626 (Dr. Hershberger).
PY - 2011/1
Y1 - 2011/1
N2 - Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18. years of age who underwent detailed clinical and genetic evaluation and have summarized here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1. year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2. weeks, 9 and 13. years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1. year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases, pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause.
AB - Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18. years of age who underwent detailed clinical and genetic evaluation and have summarized here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1. year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2. weeks, 9 and 13. years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1. year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases, pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause.
KW - Children
KW - Dilated Cardiomyopathy
KW - Genetics
KW - Infants
KW - Pediatrics
KW - Sudden Cardiac Death
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U2 - 10.1016/j.ppedcard.2010.11.008
DO - 10.1016/j.ppedcard.2010.11.008
M3 - Article
AN - SCOPUS:79451474239
VL - 31
SP - 39
EP - 47
JO - Progress in Pediatric Cardiology
JF - Progress in Pediatric Cardiology
SN - 1058-9813
IS - 1
ER -