Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes.
BACKGROUND
Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality.


METHODS
This study aimed to identify the mutation present in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy.


RESULTS
In all four, a novel mitochondrial m.8528T-->C mutation was identified. This results in a change of the initiation codon in ATPase 6 to threonine and a concurrent change from a highly conserved hydrophobic amino acid, tryptophan, at position 55 of ATPase 8 to a highly basic arginine. To our knowledge, this is the first report of a mutation affecting both mitochondrial genome-encoded complex V subunit proteins. Testing of the relatives of one patient indicated that the mutation is heteroplasmic and correlated with disease.


CONCLUSIONS
Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.
Ware
S M
SM
Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. stephanie.ware@cchmc.org
El-Hassan
N
N
Kahler
S G
SG
Zhang
Q
Q
Ma
Y-W
YW
Miller
E
E
Wong
B
B
Spicer
R L
RL
Craigen
W J
WJ
Kozel
B A
BA
Grange
D K
DK
Wong
L-J
LJ
D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation
C412204:ATP synthase subunit 6; C513300:MT-ATP8 protein, human; D025261:Mitochondrial Proton-Translocating ATPases