Background: Mutations in FKTN encoding for fukutin cause Fukuyama-type congenital muscular dystrophy characterized by severe muscle wasting and hypotonia with mental retardation. Fukuyama-type congenital muscular dystrophy is a recessive genetic trait. FKTN mutations in patients with dilated cardiomyopathy (DCM) have been investigated by our research group. The patients showed hyper-CKemia with mild or no muscle weakness and without mental retardation, suggesting that the clinical spectrum of FKTN mutations are wider than previously thought. The current study was designed to further explore the association of FKTN mutations with DCM or hypertrophic cardiomyopathy (HCM).
Methods and results: A total of 172 patients with DCM, 144 patients with familial HCM and 384 control individuals were analyzed for FKTN mutations. There was a DCM patient who was a compound heterozygote of a 3-kb insertion mutation and a missense mutation Cys101Phe. The patient showed hyper-CKemia with mild muscle involvement and no brain involvement. In contrast, 2 other DCM patients and 3 controls were heterozygous for the insertion mutation and normal allele, showing that the heterozygous insertion mutation itself was not associated with DCM. No mutation was found in the HCM patients.
Conclusions: These observations indicated that the compound heterozygous FKTN mutation was a rare cause of DCM. Hyper-CKemia might be indicative of FKTN mutation in DCM.