%0 Journal Article
%A Minnerop, Martina
%A Kurzwelly, Delia
%A Wagner, Holger
%A Soehn, Anne S
%A Reichbauer, Jennifer
%A Tao, Feifei
%A Rattay, Tim W
%A Peitz, Michael
%A Rehbach, Kristina
%A Giorgetti, Alejandro
%A Pyle, Angela
%A Thiele, Holger
%A Altmüller, Janine
%A Timmann, Dagmar
%A Karaca, Ilker
%A Lennarz, Martina
%A Baets, Jonathan
%A Hengel, Holger
%A Synofzik, Matthis
%A Atasu, Burcu
%A Feely, Shawna
%A Kennerson, Marina
%A Stendel, Claudia
%A Lindig, Tobias
%A Gonzalez, Michael A
%A Stirnberg, Rüdiger
%A Sturm, Marc
%A Röske, Sandra
%A Jung, Johanna
%A Bauer, Peter
%A Lohmann, Ebba
%A Herms, Stefan
%A Heilmann-Heimbach, Stefanie
%A Nicholson, Garth
%A Mahanjah, Muhammad
%A Sharkia, Rajech
%A Carloni, Paolo
%A Brüstle, Oliver
%A Klopstock, Thomas
%A Mathews, Katherine D
%A Shy, Michael E
%A de Jonghe, Peter
%A Chinnery, Patrick F
%A Horvath, Rita
%A Kohlhase, Jürgen
%A Schmitt, Ina
%A Wolf, Michael
%A Greschus, Susanne
%A Amunts, Katrin
%A Maier, Wolfgang
%A Schöls, Ludger
%A Nürnberg, Peter
%A Zuchner, Stephan
%A Klockgether, Thomas
%A Ramirez, Alfredo
%A Schüle, Rebecca
%T Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.
%J Brain
%V 140
%N 6
%@ 0006-8950
%C Oxford
%I Oxford Univ. Press
%M DZNE-2020-05625
%P 1561-1578
%D 2017
%X Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1
%K Aged
%K Cell Culture Techniques
%K Exons: genetics
%K Female
%K Genetic Association Studies
%K Humans
%K Induced Pluripotent Stem Cells
%K Intellectual Disability: diagnostic imaging
%K Intellectual Disability: genetics
%K Intellectual Disability: physiopathology
%K Introns: genetics
%K Male
%K Middle Aged
%K Muscle Spasticity: diagnostic imaging
%K Muscle Spasticity: genetics
%K Muscle Spasticity: physiopathology
%K Mutation
%K Optic Atrophy: diagnostic imaging
%K Optic Atrophy: genetics
%K Optic Atrophy: physiopathology
%K Pedigree
%K Phenotype
%K RNA Polymerase III: genetics
%K Spastic Paraplegia, Hereditary: diagnostic imaging
%K Spastic Paraplegia, Hereditary: genetics
%K Spastic Paraplegia, Hereditary: physiopathology
%K Spinocerebellar Ataxias: diagnostic imaging
%K Spinocerebellar Ataxias: genetics
%K Spinocerebellar Ataxias: physiopathology
%K POLR3A protein, human (NLM Chemicals)
%K RNA Polymerase III (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28459997
%2 pmc:PMC6402316
%R 10.1093/brain/awx095
%U https://pub.dzne.de/record/139303