title: Mitochondrial DNA deletions detected by Multiplex Ligation-dependent Probe Amplification.
abstract: The genetic diagnosis algorithm for mitochondrial (mt) diseases starts looking for deletions and common mutations in mtDNA. MtDNA's special features, such as large and variable genome copies, heteroplasmy, polymorphisms, and its duplication in the nuclear genome as pseudogenes (NUMTs), make it vulnerable to diagnostic misleading interpretations. Multiplex Ligation-dependent Probe Amplification (MLPA) is used to detect copy number variations in nuclear genes and its application on mtDNA has not been widely spread. We report three Kearns Sayre Syndrome patients and one Chronic Progressive External Ophthalmoplegia adult, whose diagnostic mtDNA deletions were detected by MLPA using a very low amount of DNA. This managed to "dilute" the NUMT interference as well as enhance MLPA's efficiency. By this report, we conclude that when MLPA is performed upon a reduced amount of DNA, it can detect effectively mtDNA deletions. We propose MLPA as a possible first step method in the diagnosis of mt diseases.
authors.affiliation: a IHEM CCT-CONICET and National University of Cuyo , Mendoza , Argentina .
authors.forename: Lía
authors.initials: L
authors.lastname: Mayorga
authors.affiliation: a IHEM CCT-CONICET and National University of Cuyo , Mendoza , Argentina .
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Laurito
authors.affiliation: b Garrahan Children's Hospital , Buenos Aires , Argentina .
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Loos
authors.affiliation: b Garrahan Children's Hospital , Buenos Aires , Argentina .
authors.forename: Hernán D
authors.initials: HD
authors.lastname: Eiroa
authors.affiliation: b Garrahan Children's Hospital , Buenos Aires , Argentina .
authors.forename: Silvina
authors.initials: S
authors.lastname: de Pinho
authors.affiliation: b Garrahan Children's Hospital , Buenos Aires , Argentina .
authors.forename: Fabiana
authors.initials: F
authors.lastname: Lubieniecki
authors.affiliation: b Garrahan Children's Hospital , Buenos Aires , Argentina .
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Arroyo
authors.affiliation: c Notti Children's Hospital , Mendoza , Argentina , and.
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pereyra
authors.affiliation: d J.M. Ramos Mejía General Hospital , Buenos Aires , Argentina.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Kauffman
authors.affiliation: a IHEM CCT-CONICET and National University of Cuyo , Mendoza , Argentina .
authors.forename: María
authors.initials: M
authors.lastname: Roqué
mesh_terms: D000465:Algorithms; D056915:DNA Copy Number Variations / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*
chemical_list: D004272:DNA, Mitochondrial
keywords: Chronic progressive external ophthalmoplegia; Kearns Sayre Syndrome; NUMTs; copy number changes; diagnosis; mitochondrial disease