title: A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.
abstract: Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.
authors.affiliation: a Department of Biochemistry and Molecular Biology , Fourth Military Medical University , Xi'an , Shaanxi , China .|b Center for DNA Typing, Fourth Military Medical University , Xi'an , Shaanxi , China .
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Chen
authors.affiliation: c Department of Neurology , Xi'an Children's Hospital , Xi'an , Shaanxi , China .
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Zhao
authors.affiliation: c Department of Neurology , Xi'an Children's Hospital , Xi'an , Shaanxi , China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: c Department of Neurology , Xi'an Children's Hospital , Xi'an , Shaanxi , China .
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: d Second Affiliated Hospital of Shaanxi College of Chinese Medicine , Xianyang , Shaanxi , China , and.
authors.forename: Chang-Hu
authors.initials: CH
authors.lastname: Dong
authors.affiliation: a Department of Biochemistry and Molecular Biology , Fourth Military Medical University , Xi'an , Shaanxi , China .|b Center for DNA Typing, Fourth Military Medical University , Xi'an , Shaanxi , China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: e Department of Endocrinology and Metabolism , Xi'an Children's Hospital , Xi'an , Shaanxi , China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: a Department of Biochemistry and Molecular Biology , Fourth Military Medical University , Xi'an , Shaanxi , China .|b Center for DNA Typing, Fourth Military Medical University , Xi'an , Shaanxi , China .
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Wu
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency* / Q000235:genetics; D015415:Biomarkers; D000080984:Congenital Bone Marrow Failure Syndromes; D004272:DNA, Mitochondrial; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D009135:Muscular Diseases / Q000175:diagnosis* / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D044942:Acyl-CoA Dehydrogenase, Long-Chain
keywords: Mitochondrial DNA/nuclear DNA genome ratio; Pearson syndrome; mtDNA deletion load; neonatal diabetes mellitus