Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy

• Published in: Brain & development (Tokyo. 1979) 2014-05, Vol.36 (5), p.394-398
• Main Authors: Ma, Yan-Yan, Wu, Tong-Fei, Liu, Yu-Peng, Wang, Qiao, Li, Xi-Yuan, Ding, Yuan, Song, Jin-Qing, Shi, Xiu-Yu, Zhang, Wei-Na, Zhao, Meng, Hu, Ling-Yan, Ju, Jun, Wang, Zhi-Long, Yang, Yan-Ling, Zou, Li-Ping
• Format: Article
• Language: English
• Subjects: Base Sequence; Brain - pathology; Child; China; DNA Mutational Analysis; Electron Transport Complex II - deficiency; Electron Transport Complex II - genetics; Electron Transport Complex II - metabolism; Frame-shift mutation; Frameshift Mutation; Humans; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors - diagnosis; Metabolism, Inborn Errors - genetics; Metabolism, Inborn Errors - metabolism; Metabolism, Inborn Errors - pathology; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; Neurology; Respiratory chain complex II deficiency; SDHA gene
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2013.06.003

Abstract Objective: To investigate respiratory chain complex II deficiency resulted from mutation in succinate dehydrogenase gene (SDH) encoding complex II subunits in China. Methods: An 11-year-old boy was admitted to our hospital. He had a history of progressive psychomotor regression and weakness since the age of 4 years. His cranial magnetic resonance imaging revealed focal, bilaterally symmetrical lesions in the basal ganglia and thalamus, indicating mitochondrial encephalopathy. The activities of mitochondrial respiratory chain enzymes I−V in peripheral leukocytes were determined via spectrophotometry. Mitochondrial DNA and the succinate dehydrogenase A ( SDHA ) gene were analyzed by direct sequencing. Results: Complex II activity in the leukocytes had decreased to 33.07 nmol/min/mg mitochondrial protein (normal control 71.8 ± 12.9); the activities of complexes I, III, IV and V were normal. The entire sequence of the mitochondrial DNA was normal. The SDHA gene showed two heterozygous frame-shift mutations: c.G117G/del in exon 2 and c.T220T/insT in exon 3, which resulted in stop codons at residues 56 and 81, respectively. Conclusions: We have described the first Chinese case of mitochondrial respiratory chain complex II deficiency, which was diagnosed using enzyme assays and gene analysis. Two novel, compound, frame-shift mutations, c.G117G/del in exon 2 and c.T220T/insT in exon 3 of the SDHA gene, were found in our patient.