TY - JOUR
T1 - Lamin A/C gene mutations in familial cardiomyopathy with advanced atrioventricular block and arrhythmia
AU - Saga, Akiko
AU - Karibe, Akihiko
AU - Otomo, Jun
AU - Iwabuchi, Kaoru
AU - Takahashi, Toshiaki
AU - Kanno, Hiroyuki
AU - Kikuchi, Junichi
AU - Keitoku, Mitsumasa
AU - Shinozaki, Tsuyoshi
AU - Shimokawa, Hiroaki
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Atrioventricular block
KW - Cardiomyopathy
KW - Molecular genetics
KW - Sudden death
KW - Ventricular tachycardia
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U2 - 10.1620/tjem.218.309
DO - 10.1620/tjem.218.309
M3 - Article
C2 - 19638735
AN - SCOPUS:70349773848
VL - 218
SP - 309
EP - 316
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 4
ER -