Clinical phenotype and genotype analysis in 61 patients with large scale single deletion in mitochondrial DNA

Objective To investigate the clinical and genetic characteristics of a cohort of Chinese patients with large-scale single in mitochondrial DNA (mtDNA). Methods Long-range PCR was performed to search large scale deletions in 70 patients' muscle mtDNA who were diagnosed with mitochondrial disease by clinical and muscle pathological examination. Then multiple restriction enzyme digestion of long-range PCR product followed by short-cycle PCR were used to define the exact size and location of large-scale deletions. We summarized the clinical phenotypes of patients, and analyzed the correlations between clinical phenotypes and size of mtDNA deletions in those patients with single large-scale deletion. Results Sixty-one patients were identified to have single large-scale in their muscle mtDNA, including 54 patients with chronic progressive external ophthalmoplegia (CPEO), 6 with Kearns-Sayre syndrome (KSS) and 1 with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Totally 37 patterns of mtDNA deletions were detected in this cohort of patients. The deletion , 4 977 bp appeared in 39.3%(24/61) patients. The mean size of single in CPEO patients was (5 052.17±1 390.96) bp, while in KSS patients it was (5 912.43±1 262.15) bp. There was no significant difference between CPEO patients group and KSS patients group. The size of deletions was correlated with onset age (r=-0.415, P=0.001). Conclusions Large-scale single of mtDNA mainly causes CPEO and KSS. Patients with larger deletions present with earlier onset of disease. The mtDNA deletion is also common in Chinese patients. Key words: Ophthalmoplegia, chronic progressive external; Kearns-Sayre syndrome; DNA, mitochondrial; Phenotype; Genotype; Polymerase chain reaction