Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy

Keiichi Hirono, Yukiko Hata, Makoto Nakazawa, Nobuo Momoi, Tohru Tsuji, Taro Matsuoka, Mamoru Ayusawa, Yuriko Abe, Tamaki Hayashi, Nobuyuki Tsujii, Tadaaki Abe, Heima Sakaguchi, Ce Wang, Asami Takasaki, Shinya Takarada, Mako Okabe, Nariaki Miyao, Hideyuki Nakaoka, Keijiro Ibuki, Kazuyoshi Saito, Sayaka Ozawa, Naoki Nishida, Neil E Bowles, Fukiko Ichida

Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.