@article{oai:nagasaki-u.repo.nii.ac.jp:00010380,
 author = {Makita, Naomasa and Seki, Akiko and Sumitomo, Naokata and Chkourko, Halina and Fukuhara, Shigetomo and Watanabe, Hiroshi and Shimizu, Wataru and Bezzina, Connie R. and Hasdemir, Can and Mugishima, Hideo and Makiyama, Takeru and Baruteau, Alban and Baron, Estelle and Horie, Minoru and Hagiwara, Nobuhisa and Wilde, Arthur A.M. and Probst, Vincent and Le, Marec  Hervé and Roden, Dan M. and Mochizuki, Naoki and Schott, Jean-Jacques and Delmar, Mario},
 issue = {1},
 journal = {Circulation: Arrhythmia and Electrophysiology},
 month = {Feb},
 note = {Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P <0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system., Circulation: Arrhythmia and Electrophysiology, 5(1), pp.163-172; 2012},
 pages = {163--172},
 title = {A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I},
 volume = {5},
 year = {2012}
}