TY  - JOUR
AU  - Minnerop, Martina
AU  - Kurzwelly, Delia
AU  - Wagner, Holger
AU  - Soehn, Anne S
AU  - Reichbauer, Jennifer
AU  - Tao, Feifei
AU  - Rattay, Tim W
AU  - Peitz, Michael
AU  - Rehbach, Kristina
AU  - Giorgetti, Alejandro
AU  - Pyle, Angela
AU  - Thiele, Holger
AU  - Altmüller, Janine
AU  - Timmann, Dagmar
AU  - Karaca, Ilker
AU  - Lennarz, Martina
AU  - Baets, Jonathan
AU  - Hengel, Holger
AU  - Synofzik, Matthis
AU  - Atasu, Burcu
AU  - Feely, Shawna
AU  - Kennerson, Marina
AU  - Stendel, Claudia
AU  - Lindig, Tobias
AU  - Gonzalez, Michael A
AU  - Stirnberg, Rüdiger
AU  - Sturm, Marc
AU  - Röske, Sandra
AU  - Jung, Johanna
AU  - Bauer, Peter
AU  - Lohmann, Ebba
AU  - Herms, Stefan
AU  - Heilmann-Heimbach, Stefanie
AU  - Nicholson, Garth
AU  - Mahanjah, Muhammad
AU  - Sharkia, Rajech
AU  - Carloni, Paolo
AU  - Brüstle, Oliver
AU  - Klopstock, Thomas
AU  - Mathews, Katherine D
AU  - Shy, Michael E
AU  - de Jonghe, Peter
AU  - Chinnery, Patrick F
AU  - Horvath, Rita
AU  - Kohlhase, Jürgen
AU  - Schmitt, Ina
AU  - Wolf, Michael
AU  - Greschus, Susanne
AU  - Amunts, Katrin
AU  - Maier, Wolfgang
AU  - Schöls, Ludger
AU  - Nürnberg, Peter
AU  - Zuchner, Stephan
AU  - Klockgether, Thomas
AU  - Ramirez, Alfredo
AU  - Schüle, Rebecca
TI  - Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.
JO  - Brain
VL  - 140
IS  - 6
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-05625
SP  - 1561-1578
PY  - 2017
AB  - 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
KW  - Aged
KW  - Cell Culture Techniques
KW  - Exons: genetics
KW  - Female
KW  - Genetic Association Studies
KW  - Humans
KW  - Induced Pluripotent Stem Cells
KW  - Intellectual Disability: diagnostic imaging
KW  - Intellectual Disability: genetics
KW  - Intellectual Disability: physiopathology
KW  - Introns: genetics
KW  - Male
KW  - Middle Aged
KW  - Muscle Spasticity: diagnostic imaging
KW  - Muscle Spasticity: genetics
KW  - Muscle Spasticity: physiopathology
KW  - Mutation
KW  - Optic Atrophy: diagnostic imaging
KW  - Optic Atrophy: genetics
KW  - Optic Atrophy: physiopathology
KW  - Pedigree
KW  - Phenotype
KW  - RNA Polymerase III: genetics
KW  - Spastic Paraplegia, Hereditary: diagnostic imaging
KW  - Spastic Paraplegia, Hereditary: genetics
KW  - Spastic Paraplegia, Hereditary: physiopathology
KW  - Spinocerebellar Ataxias: diagnostic imaging
KW  - Spinocerebellar Ataxias: genetics
KW  - Spinocerebellar Ataxias: physiopathology
KW  - POLR3A protein, human (NLM Chemicals)
KW  - RNA Polymerase III (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28459997
C2  - pmc:PMC6402316
DO  - DOI:10.1093/brain/awx095
UR  - https://pub.dzne.de/record/139303
ER  -