Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3001 Berne, Switzerland.
Genomics. 2011 Jan;97(1):51-7. doi: 10.1016/j.ygeno.2010.09.005. Epub 2010 Oct 12.
Cardiomyopathies are severe degenerative disorders of the myocardium that lead to heart failure. During the last three decades bovine dilated cardiomyopathy (BDCMP) was observed worldwide in cattle of Holstein-Friesian origin. In the Swiss cattle population BDCMP affects Fleckvieh and Red Holstein breeds. The heart of affected animals is enlarged due to dilation of both ventricles. Clinical signs are caused by systolic dysfunction and affected individuals die as a result of severe heart insufficiency. BDCMP follows an autosomal recessive pattern of inheritance and the disease-causing locus was mapped to bovine chromosome 18 (BTA18). In the present study we describe the successful identification of the causative mutation in the OPA3 gene located on BTA18 that was previously reported to cause 3-methylglutaconic aciduria type III in Iraqi-Jewish patients. We demonstrated conclusive genetic and functional evidence that the nonsense mutation c.343C>T in the bovine OPA3 gene causes the late-onset dilated cardiomyopathy in Red Holstein cattle.
扩张型心肌病是一种严重的心肌退行性疾病，可导致心力衰竭。在过去的三十年中，荷斯坦-弗里森牛起源的牛扩张型心肌病（BDCMP）在世界范围内被观察到。在瑞士牛群中，BDCMP 影响弗莱维赫和红荷斯坦品种。患病动物的心脏因两个心室扩张而增大。临床症状是由收缩功能障碍引起的，受影响的个体因严重的心脏功能不全而死亡。BDCMP 遵循常染色体隐性遗传模式，致病基因座定位于牛染色体 18（BTA18）。在本研究中，我们成功鉴定了位于 BTA18 上的 OPA3 基因中的致病突变，该突变先前被报道可导致伊拉克-犹太患者的 3-甲基戊烯二酸尿症 III 型。我们证明了确凿的遗传和功能证据，即牛 OPA3 基因中的无义突变 c.343C>T 导致红荷斯坦牛的迟发性扩张型心肌病。
