A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death
A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death
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DOI：
10.1007/s00439-019-01973-2
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发表时间：
2019-05-01
期刊：
影响因子：
5.3
通讯作者：
Granzier, Henk
中科院分区：
文献类型：
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作者：
Meurs, Kathryn M.;Friedenberg, Steven G.;Granzier, Henk
该狗提供了家族性扩张型心肌病的大型动物模型，用于研究这种常见家族性心血管疾病的重要方面。我们之前已经在杜宾犬品种中证明了一种犬扩张型心肌病，它作为常染色体显性性状遗传，并与丙酮酸脱氢酶激酶4 (PDK4) 基因中的剪接位点变异相关，然而，该物种也存在遗传异质性，并非所有受影响的狗都具有PDK4变异。对患有扩张型心肌病和心源性猝死且无 PDK4 变异的杜宾犬家族进行全基因组测序。鉴定出位于该分子 I 带跨越区域的免疫球蛋白样结构域的 titin 基因中的病理性错义变异，该变异与该疾病高度相关（p
The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p