Parkinsonism, cognitive deficit and behavioural disturbance caused by a novel mutation in the polymerase gamma gene

• Published in: Journal of the neurological sciences 2015-03, Vol.350 (1), p.93-97
• Main Authors: Delgado-Alvarado, Manuel, de la Riva, Patricia, Jiménez-Urbieta, Haritz, Gago, Belén, Gabilondo, Alazne, Bornstein, Belén, Rodríguez-Oroz, María Cruz
• Format: Article
• Language: English
• Subjects: Aged, 80 and over; Cognition Disorders - diagnosis; Cognition Disorders - genetics; Cognitive impairment; DNA Polymerase gamma; DNA, Mitochondrial - genetics; DNA-Directed DNA Polymerase - genetics; Female; Humans; Mental Disorders - diagnosis; Mental Disorders - genetics; Mutation - genetics; Neurology; Obsessive disorder; Parkinsonian Disorders - diagnosis; Parkinsonian Disorders - genetics; Parkinsonism; POLG; Progressive external ophthalmoplegia; Ptosis
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2015.02.011

Abstract Polymerase γ (POLG) is the enzyme responsible for the replication and maintenance of mitochondrial DNA (mtDNA). Mutations in the POLG1 gene can lead to mitochondrial dysfunction, producing a wide range of neurological and non-neurological phenotypes. Neurological manifestations include ataxia, muscular weakness, epilepsy, progressive external ophthalmoplegia (PEO), ptosis, neuropathy, psychiatric disorders and, more rarely, parkinsonism. We present the case of an 80-year old female patient with a history of PEO, ptosis, childish behaviour, obsessive disorder, cognitive decline, and parkinsonism. A comprehensive study showed striatal dopamine deficiency on DaT Scan and ragged red fibres as evidenced by Gomori staining in a biopsy of the biceps brachii. Multiple deletions of mtDNA were detected, and sequencing of the POLG1 gene identified a novel substitution, 2834A > T, in exon 18, changing the p.His945Leu amino acid. In silico analysis using PolyPhen-2 ( http://genetics.bwh.hardvard.edu/pph2/ ) predicted that this change is probably damaging, with a score of 1.0 (0–1).