Whole-exome sequencing reveals a novel mutation of MT-ND5 gene in a mitochondrial cardiomyopathy pedigree: Patients who show biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance

Zhou, Nianwei; Tang, Lu; Jiang, Yingying; Qin, Shengmei; Cui, Jie; Wang, Yanan; Zhu, Wenqing; Zhao, Weipeng; Pan, Cuizhen; Shu, Xianhong

doi:10.14744/AnatolJCardiol.2018.53258

Original Investigation

Whole-exome sequencing reveals a novel mutation of MT-ND5 gene in a mitochondrial cardiomyopathy pedigree: Patients who show biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance

Nianwei Zhou ¹ , Lu Tang ¹ , Yingying Jiang ¹ , Shengmei Qin ² , Jie Cui ² , Yanan Wang ¹ , Wenqing Zhu ² , Weipeng Zhao ¹ , Cuizhen Pan ¹ , Xianhong Shu ¹

¹Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai Institute of Medical Imaging; Shanghai-China
²Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai Institute of Medical Imaging; Shanghai-China

Anatol J Cardiol 2019; 21(1): 18-24 PubMed ID: 30587702 DOI: 10.14744/AnatolJCardiol.2018.53258

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Abstract

Objective: The aim of the present study was to determine whether pathogenic mutations were present in families with mitochondrial cardiomyopathy that presented during adolescence.
Methods: The proband was a 21-year-old man who presented clinically with palpitations, chest tightness, pulmonary hypertension, and limited exercise tolerance. Cardiac magnetic resonance imaging studies showed biventricular cardiac hypertrophy. We determine whether pathogenic mutations were present by whole-exome sequencing (WES) in families.
Results: Screening of the family using tandem mass spectrometry showed elevated lactic acid levels, glutaric aciduria, a mildly increased glutarylcarnitine-to-octanoylcarnitine ratio, and normal blood α-glucosidase, which was consistent with a respiratory chain complex 1 metabolic disorder. We identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala). Skeletal muscle biopsy histology showed predominantly ragged red fibers and few ragged blue fibers, which was consistent with mitochondrial myopathy.
Conclusion: In the present study, we identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala), in a family pedigree using WES.

Keywords: MT-ND5, whole-exome sequencing, cardiomyopathy, pulmonary hypertension