The Importance of Genetic Counseling, DNA Diagnostics, and Cardiologic Family Screening in Left Ventricular Noncompaction Cardiomyopathy
The Importance of Genetic Counseling, DNA Diagnostics, and Cardiologic Family Screening in Left Ventricular Noncompaction Cardiomyopathy
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DOI：
10.1161/circgenetics.109.903898
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发表时间：
2010-06-01
影响因子：
--
通讯作者：
Majoor-Krakauer, Danielle F.
中科院分区：
文献类型：
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作者：
Hoedemaekers, Yvonne M.;Caliskan, Kadir;Majoor-Krakauer, Danielle F.
背景-左心室致密化不全是一种独特的心肌病，其特征是左心室壁双层增厚，由厚的内膜层和明显的小梁间凹以及薄而致密的心外膜层组成。与肥大性和扩张性心肌病类似，LVNC具有遗传异质性，最近发现与肌节基因突变有关。为了有助于LVNC的遗传分类，一个系统的心脏家族研究进行了一个队列的58个连续诊断和分子筛选孤立LVNC（49名成人和9名儿童）。方法和结果相结合的分子检测和心脏家族筛查显示，67%的LVNC是遗传性的。对50名无血缘关系的LVNC先证者的194名亲属进行心电图和超声心动图心脏病筛查，发现32个家族（64%）有家族性心肌病，包括LVNC、肥厚型心肌病和扩张型心肌病。新诊断为心肌病的亲属中有63%没有症状。在17名无症状的突变亲属中，9名患有致密化不全型心肌病。8例携带者未检出。这可能解释了44%（14/32）的家族性疾病在心脏病家族筛查前未被家族史发现。对17个基因的分子筛选在41%（56人中的23人）的受试先证者、35%（48人中的17人）的成人和8名儿童中的6人中发现了11个基因的突变。在18个家庭中，单突变以常染色体显性遗传模式传播。2例成人和2例儿童为2种不同突变的复合或双杂合子。1例成年先证者有3个突变。在50%（16 32）的家族性LVNC，遗传缺陷仍然inconclusion.Conclusion-LVNC主要是一种遗传性心肌病，从无症状到严重的变量介绍。因此，LVNC的诊断需要遗传咨询，DNA诊断和心脏病家族筛查。(Circ Genet. 2010; 3：232-239）。
Background-Left ventricular (LV) noncompaction (LVNC) is a distinct cardiomyopathy featuring a thickened bilayered LV wall consisting of a thick endocardial layer with prominent intertrabecular recesses with a thin, compact epicardial layer. Similar to hypertrophic and dilated cardiomyopathy, LVNC is genetically heterogeneous and was recently associated with mutations in sarcomere genes. To contribute to the genetic classification for LVNC, a systematic cardiological family study was performed in a cohort of 58 consecutively diagnosed and molecularly screened patients with isolated LVNC (49 adults and 9 children).Methods and Results-Combined molecular testing and cardiological family screening revealed that 67% of LVNC is genetic. Cardiological screening with electrocardiography and echocardiography of 194 relatives from 50 unrelated LVNC probands revealed familial cardiomyopathy in 32 families (64%), including LVNC, hypertrophic cardiomyopathy, and dilated cardiomyopathy. Sixty-three percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic. Of 17 asymptomatic relatives with a mutation, 9 had noncompaction cardiomyopathy. In 8 carriers, nonpenetrance was observed. This may explain that 44% (14 of 32) of familial disease remained undetected by ascertainment of family history before cardiological family screening. The molecular screening of 17 genes identified mutations in 11 genes in 41% (23 of 56) tested probands, 35% (17 of 48) adults and 6 of 8 children. In 18 families, single mutations were transmitted in an autosomal dominant mode. Two adults and 2 children were compound or double heterozygous for 2 different mutations. One adult proband had 3 mutations. In 50% (16 of 32) of familial LVNC, the genetic defect remained inconclusive.Conclusion-LVNC is predominantly a genetic cardiomyopathy with variable presentation ranging from asymptomatic to severe. Accordingly, the diagnosis of LVNC requires genetic counseling, DNA diagnostics, and cardiological family screening. (Circ Cardiovasc Genet. 2010; 3: 232-239.)