Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy

作者：Matsushita Yoshihisa; Furukawa Toru; Kasanuki Hiroshi; Nishibatake Makoto; Kurihara Yachiyo; Ikeda Atsushi; Kamatani Naoyuki; Takeshima Hiroshi; Matsuoka Rumiko^*

来源：Journal of Human Genetics, 2007, 52(6): 543-548.

DOI：10.1007/s10038-007-0149-y

• junctophilin
• hypertrophic cardiomyopathy
• Ca2+ signaling
• ryanodine receptor
• junctional membrane complexes
• Ca2+-induced Ca(2+)supercript stop release

Junctophilin subtypes, designated as JPH1-4, are protein components of junctional complexes and play essential roles in cellular Ca2+ signaling in excitable cells. Knockout mice lacking the cardiac-type Jph2 die of embryonic cardiac arrest, and the mutant cardiac myocytes exhibit impaired formation of peripheral couplings and arrhythmic Ca2+ signaling caused by functional uncoupling between dihydropyridine and ryanodine receptor channels. Based on these observations, we hypothesized that mutations of JPH2 could cause human genetic cardiac diseases. Among 195 Japanese patients (148 index cases and 47 affected family members) with hypertrophic cardiomyopathy (HCM), two heterozygous nonsynonymous nucleotide transitions, G505S and R436C, were newly found in JPH2. When Fisher's exact test was used to compare index cases with HCM to unrelated Japanese healthy controls in the frequencies of mutant alleles, only the G505S mutation showed statistical significance (4/296 HCM patients and 0/472 control individuals, P=0.022). This result was still significant after Bonferroni's correction for multiple comparisons (P=0.044). To the best of our knowledge, this is the first report on JPH2 mutation associated with HCM.

• 出版日期2007-6