Zarrouk Sinda, Finsterer Josef, Mehri Sounira, Ourda Fatma, Ben Arab Saida, Boussada Raafik
Department of Genetic and Molecular Epidemiology, Medical University of Tunis, Tunisia.
City Hospital Landstrasse, Messerli Institute, Vienna, Austria.
J Med Cases. 2021 Nov;12(11):455-459. doi: 10.14740/jmc3787. Epub 2021 Nov 5.
Mitochondrial DNA (mtDNA) mutations frequently manifest with multisystem disease, including cardiomyopathy (CM). Various studies described mutations in protein-encoding mtDNA genes, such as cytochrome-b, manifesting with CM. A detailed clinical, biochemical, and molecular genetic analysis was performed in a 40-year-old male with dilated CM (DCM) to detect the underlying mtDNA defect. Muscle biopsy showed complex-III deficiency, and sequencing of the cytochrome-b gene revealed the pathogenic variant m.14757T>C in , resulting in the replacement of the hydrophobic methionine by the polar threonine (M4T). By application of the PolyPhen algorithm the variant was predicted as pathogenic. The mutation was not found in 100 healthy controls and never reported as a neutral polymorphism despite extensive sequencing of the cytochrome-b gene in 2,704 normal healthy controls from different ethnic backgrounds. In conclusion, the novel variant m.14757T>C in is associated with DCM suggesting a pathophysiologic role of the variant in the development of DCM.
线粒体DNA（mtDNA）突变常表现为多系统疾病，包括心肌病（CM）。各种研究描述了蛋白质编码mtDNA基因中的突变，如细胞色素b，可表现为CM。对一名40岁扩张型心肌病（DCM）男性患者进行了详细的临床、生化和分子遗传学分析，以检测潜在的mtDNA缺陷。肌肉活检显示复合体III缺乏，细胞色素b基因测序揭示了致病变体m.14757T>C，导致疏水性甲硫氨酸被极性苏氨酸取代（M4T）。应用PolyPhen算法预测该变体为致病性。在100名健康对照中未发现该突变，尽管对来自不同种族背景的2704名正常健康对照的细胞色素b基因进行了广泛测序，但该突变从未被报道为中性多态性。总之，新变体m.14757T>C与DCM相关，提示该变体在DCM发生发展中具有病理生理作用。
