title: LMNA cardiomyopathy detected in Japanese arrhythmogenic right ventricular cardiomyopathy cohort.
abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease. While desmosomal gene mutations are considered major causes of ARVC, LMNA mutations have been reported to be possible causes of ARVC. In this study, we performed extensive genetic screening for LMNA mutations in our Japanese ARVC cohort to assess the prevalence and characteristics of LMNA mutation-positive ARVC cases.
  
  
  
  Our study cohort consisted of 57 ARVC probands. Genetic analyses were performed by using direct sequencing and targeted sequencing of LMNA and four desmosomal genes. We compared clinical features of probands with desmosomal gene mutations to those of probands with LMNA mutations.
  
  
  
  Among 57 clinically diagnosed ARVC probands, we identified desmosomal gene mutations in 26 probands (45.6%) and two LMNA mutations in two probands. The first LMNA mutation p.M1K was detected in a 62-year-old male proband, while the second mutation p.W514X was found in a 70-year-old male proband. Compared to the 26 probands with desmosomal gene mutations, in the two probands with LMNA mutations, the mean age at diagnosis was significantly higher, and their heart rate at the diagnosis was significantly slower. While both probands with LMNA mutations underwent pacemaker implantation, only one proband with desmosomal mutations received this treatment (2/2 vs. 1/26).
  
  
  
  Genetic screening for LMNA gene is important for ARVC patients, particularly in patients with bradycardia.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Umehara
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Nishiuchi
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan. Electronic address: horie@belle.shiga-med.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis* / Q000235:genetics*; D003896:Desmosomes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007564:Japan; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A
keywords: Arrhythmogenic right ventricular cardiomyopathy; Desmosome; LMNA; PKP2; Pacemaker therapy