title: Redefining phenotypes associated with mitochondrial DNA single deletion.
abstract: Progressive external ophthalmoplegia (PEO), Kearns-Sayre syndrome (KSS) and Pearson syndrome are the three sporadic clinical syndromes classically associated with single large-scale deletions of mitochondrial DNA (mtDNA). PEO plus is a term frequently utilized in the clinical setting to identify patients with PEO and some degree of multisystem involvement, but a precise definition is not available. The purpose of the present study is to better define the clinical phenotypes associated with a single mtDNA deletion, by a retrospective study on a large cohort of 228 patients from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". In our database, single deletions account for about a third of all patients with mtDNA-related disease, more than previously recognized. We elaborated new criteria for the definition of PEO and "KSS spectrum" (a category of which classic KSS represents the most severe extreme). The criteria for "KSS spectrum" include the resulting multisystem clinical features associated with the KSS features, and which therefore can predict their presence or subsequent development. With the new criteria, we were able to classify nearly all our single-deletion patients: 64.5% PEO, 31.6% KSS spectrum (including classic KSS 6.6%) and 2.6% Pearson syndrome. The deletion length was greater in KSS spectrum than in PEO, whereas heteroplasmy was inversely related with age at onset. We believe that the new phenotype definitions implemented here may contribute to a more homogeneous patient categorization, which will be useful in future cohort studies of natural history and clinical trials.
authors: Neurological Clinic, University of Pisa, Via Roma 67, 56126, Pisa, Italy, mancusomichelangelo@gmail.com.
authors: Michelangelo
authors: M
authors: Mancuso
authors: Daniele
authors: D
authors: Orsucci
authors: Corrado
authors: C
authors: Angelini
authors: Enrico
authors: E
authors: Bertini
authors: Valerio
authors: V
authors: Carelli
authors: Giacomo Pietro
authors: GP
authors: Comi
authors: Maria Alice
authors: MA
authors: Donati
authors: Antonio
authors: A
authors: Federico
authors: Carlo
authors: C
authors: Minetti
authors: Maurizio
authors: M
authors: Moggio
authors: Tiziana
authors: T
authors: Mongini
authors: Filippo Maria
authors: FM
authors: Santorelli
authors: Serenella
authors: S
authors: Servidei
authors: Paola
authors: P
authors: Tonin
authors: Antonio
authors: A
authors: Toscano
authors: Claudio
authors: C
authors: Bruno
authors: Luca
authors: L
authors: Bello
authors: Elena
authors: E
authors: Caldarazzo Ienco
authors: Elena
authors: E
authors: Cardaioli
authors: Michela
authors: M
authors: Catteruccia
authors: Paola
authors: P
authors: Da Pozzo
authors: Massimiliano
authors: M
authors: Filosto
authors: Costanza
authors: C
authors: Lamperti
authors: Isabella
authors: I
authors: Moroni
authors: Olimpia
authors: O
authors: Musumeci
authors: Elena
authors: E
authors: Pegoraro
authors: Dario
authors: D
authors: Ronchi
authors: Donato
authors: D
authors: Sauchelli
authors: Mauro
authors: M
authors: Scarpelli
authors: Monica
authors: M
authors: Sciacco
authors: Maria Lucia
authors: ML
authors: Valentino
authors: Liliana
authors: L
authors: Vercelli
authors: Massimo
authors: M
authors: Zeviani
authors: Gabriele
authors: G
authors: Siciliano
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency* / Q000235:genetics; D000328:Adult; D000080984:Congenital Bone Marrow Failure Syndromes; D004272:DNA, Mitochondrial / Q000235:genetics*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D044942:Acyl-CoA Dehydrogenase, Long-Chain