Kannankeril Prince J, Bhuiyan Zahurul A, Darbar Dawood, Mannens Marcel M A M, Wilde Arthur A M, Roden Dan M
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-9119, USA.
Heart Rhythm. 2006 Aug;3(8):939-44. doi: 10.1016/j.hrthm.2006.04.028. Epub 2006 May 3.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial disease, with male preponderance, characterized by progressive fibrofatty replacement of the right ventricle and ventricular arrhythmias. Mutations in plakophilin-2 (PKP2), a desmosomal protein, have been reported to underlie familial ARVC. We report a novel ARVC PKP2 mutation and present the clinical findings in three female mutation carriers.
We sequenced PKP2 from genomic DNA isolated from peripheral blood lymphocytes in a female proband who presented with cardiac arrest and in her four first-degree relatives. Clinical testing and diagnosis of ARVC was based on International Task Force criteria.
The proband was diagnosed with ARVC due to right ventricular enlargement and regional hypokinesis, along with repolarization abnormalities and frequent ventricular ectopy. A novel 28 bp insertion in exon 11 of the PKP2 gene was found which causes a frameshift in the coding region. This results in a change in the amino acid sequence of the protein with a premature stop codon at position 740. Of the four relatives, only the mother and younger sister were identified as mutation carriers. The mother was phenotypically normal, while the younger sister has repolarization abnormalities and frequent ventricular ectopy.
We report a novel PKP2 mutation that causes familial ARVC. All mutation carriers in this kindred group were women, and the family showed incomplete penetrance and variable expression of ARVC. Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the ARVC phenotype.
致心律失常性右室心肌病（ARVC）是一种家族性疾病，男性居多，其特征为右心室进行性纤维脂肪替代和室性心律失常。据报道，桥粒蛋白盘状球蛋白2（PKP2）突变是家族性ARVC的发病基础。我们报告了一种新的ARVC PKP2突变，并展示了三名女性突变携带者的临床发现。
我们对一名出现心脏骤停的女性先证者及其四名一级亲属外周血淋巴细胞分离的基因组DNA进行了PKP2测序。ARVC的临床检测和诊断基于国际工作组标准。
先证者因右心室扩大、节段性运动减弱，伴有复极异常和频发室性早搏而被诊断为ARVC。在PKP2基因第11外显子中发现了一个新的28bp插入，导致编码区移码。这导致蛋白质氨基酸序列改变，在第740位出现过早终止密码子。在四名亲属中，只有母亲和妹妹被确定为突变携带者。母亲表型正常，而妹妹有复极异常和频发室性早搏。
我们报告了一种导致家族性ARVC的新的PKP2突变。该家族所有突变携带者均为女性，且该家族显示出ARVC不完全外显和可变表达。盘状球蛋白2蛋白的过早截断似乎是PKP2突变引发ARVC表型的主要机制。
