Lamin A/C gene mutations in familial cardiomyopathy with advanced atrioventricular block and arrhythmia

Akiko Saga, Akihiko Karibe, Jun Otomo, Kaoru Iwabuchi, Toshiaki Takahashi, Hiroyuki Kanno, Junichi Kikuchi, Mitsumasa Keitoku, Tsuyoshi Shinozaki, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Lamin A and C proteins, encoded by the lamin A/C gene (LMNA), are inner nuclear membrane proteins predominantly expressed in terminally differentiated cells. Mutations in LMNA can cause various forms of cardiomyopathy with arrhythmia in an autosomal dominant manner. We collected and evaluated the clinical characteristics of unclassified familial cardiomyopathy with advanced AV block and sporadic cases with advanced AV block. Mutation in LMNA was directly screened using the cycle sequencing method in 5 probands of the familial cardiomyopathy and 60 sporadic cases with advanced AV block. In four of the five familial cases (80%), we identified four distinct mutations: two protein-truncation mutations, R225X and 815-818delinsCCAGAC, and two missense mutations, Y259H and R166P. No sporadic cases carried LMNA mutation. Left ventricular end-diastolic diameter (LVEDD) was slightly enlarged in LMNA mutant carriers (123.5 ± 9.5%) as well as in non-carriers (125.1 ± 13.3%), while left ventricular fractional shortening (LVFS) was preserved in LMNA mutant carriers (32.3 ± 4.8%) and non-carriers (37.6 ± 6.8%). In LMNA mutation carriers, the average age at onset of advanced AV block is significantly lower than that in non-carriers (43.7 ± 9.5 vs. 65.3 ± 13 yr., p < 0.01). Ventricular tachycardia, sudden death, and poor prognosis were observed in LMNA mutation carriers. LMNA mutation could cause familial cardiomyopathy with insignificant LV remodeling, early-age onset of advanced AV block, and lethal ventricular arrhythmia. Screening of LMNA mutation might be beneficial for risk stratification and clinical management of this type of unclassified familial cardiomyopathy.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalTohoku Journal of Experimental Medicine
Issue number4
Publication statusPublished - 2009
Externally publishedYes


  • Atrioventricular block
  • Cardiomyopathy
  • Molecular genetics
  • Sudden death
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Lamin A/C gene mutations in familial cardiomyopathy with advanced atrioventricular block and arrhythmia'. Together they form a unique fingerprint.

Cite this