title: Large copy number variations in combination with point mutations in the TYMP and SCO2 genes found in two patients with mitochondrial disorders.
abstract: Mitochondrial disorders are caused by defects in mitochondrial or nuclear DNA. Although the existence of large deletions in mitochondrial DNA (mtDNA) is well known, deletions affecting whole genes are not commonly described in patients with mitochondrial disorders. Based on the results of whole-genome analyses, copy number variations (CNVs) occur frequently in the human genome and may overlap with many genes associated with clinical phenotypes. We report the discovery of two large heterozygous CNVs on 22q13.33 in two patients with mitochondrial disorders. The first patient harboured a novel point mutation c.667G>A (p.D223N) in the SCO2 gene in combination with a paternally inherited 87-kb deletion. As hypertrophic cardiomyopathy (HCMP) was not documented in the patient, this observation prompted us to compare his clinical features with all 44 reported SCO2 patients in the literature. Surprisingly, the review shows that HCMP was present in only about 50% of the SCO2 patients with non-neonatal onset. In the second patient, who had mitochondrial neurogastrointestinal encephalopathy (MNGIE), a maternally inherited 175-kb deletion and the paternally inherited point mutation c.261G>T (p.E87D) in the TYMP gene were identified.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Alžběta
authors.initials: A
authors.lastname: Vondráčková
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Veselá
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kratochvílová
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Kučerová Vidrová
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Vinšová
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Stránecký
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Honzík
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Hansíková
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Zeman
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Tesařová
mesh_terms: D024741:Cardiomyopathy, Hypertrophic, Familial / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations; D006801:Humans; D007223:Infant; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018832:Molecular Chaperones; D039141:Muscular Dystrophy, Oculopharyngeal; D009886:Ophthalmoplegia / Q000151:congenital; D017354:Point Mutation; D013939:Thymidine Phosphorylase / Q000235:genetics*; D028361:Mitochondrial Diseases
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C400285:SCO2 protein, human; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase