BACKGROUND: Mutations in polymerase gamma cause progressive external ophthalmoplegia and a variety of associated symptoms and signs, including neuropathy, ataxia, hypogonadism, hearing loss, muscle weakness, and psychiatric problems. Extrapyramidal signs have been rarely described. OBJECTIVE: To describe a family with a novel polymerase gamma mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism. DESIGN: Case report. PATIENTS: The proband, a 49-year-old woman with incipient parkinsonism, and her 59-year-old brother with overt parkinsonian features. MAIN OUTCOME MEASURES: Mutation in the proband by sequencing the polymerase gamma gene and in affected relatives by restriction fragment length polymorphism analysis. RESULTS: We found multiple mitochondrial DNA deletions in the proband's muscle and a novel missense mutation in the polymerase gamma gene (A2492G) in the proband and in her affected siblings. CONCLUSION: Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gamma gene.
BACKGROUND: Mutations in polymerase gamma cause progressive external ophthalmoplegia and a variety of associated symptoms and signs, including neuropathy, ataxia, hypogonadism, hearing loss, muscle weakness, and psychiatric problems. Extrapyramidal signs have been rarely described. OBJECTIVE: To describe a family with a novel polymerase gamma mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism. DESIGN: Case report. PATIENTS: The proband, a 49-year-old woman with incipient parkinsonism, and her 59-year-old brother with overt parkinsonian features. MAIN OUTCOME MEASURES: Mutation in the proband by sequencing the polymerase gamma gene and in affected relatives by restriction fragment length polymorphism analysis. RESULTS: We found multiple mitochondrial DNA deletions in the proband's muscle and a novel missense mutation in the polymerase gamma gene (A2492G) in the proband and in her affected siblings. CONCLUSION:Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gamma gene.
Authors: Tjitske Kleefstra; Saskia B Wortmann; Richard J T Rodenburg; Ernie M H F Bongers; Kinga Hadzsiev; Cees Noordam; Lambert P van den Heuvel; Willy M Nillesen; Katalin Hollody; Gabrielle Gillessen-Kaesbach; Martin Lammens; Jan A M Smeitink; Ineke van der Burgt; Eva Morava Journal: Eur J Hum Genet Date: 2010-11-10 Impact factor: 4.246
Authors: Lee-Jun C Wong; Robert K Naviaux; Nicola Brunetti-Pierri; Qing Zhang; Eric S Schmitt; Cavatina Truong; Margherita Milone; Bruce H Cohen; Beverly Wical; Jaya Ganesh; Alice A Basinger; Barbara K Burton; Kathryn Swoboda; Donald L Gilbert; Adeline Vanderver; Russell P Saneto; Bruno Maranda; Georgianne Arnold; Jose E Abdenur; Paula J Waters; William C Copeland Journal: Hum Mutat Date: 2008-09 Impact factor: 4.878