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Ann Neurol. 2018 Jun;83(6):1089-1095. doi: 10.1002/ana.25204. Epub 2018 Apr 10.

Recessive mutations in VPS13D cause childhood onset movement disorders.

Author information

1
Molecular Diagnostic Laboratory and Division of Medical Genetics, Department of Pediatrics, Saint Justine University Hospital Center, Montreal, Canada.
2
Department of Neuroscience, University of Montreal, Montreal, Canada.
3
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4
Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL.
5
Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
6
Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany.
7
Institute of Human Genetics, Technical University Munich, Munich, Germany.
8
Maine Medical Partners Pediatric Specialty Care, Portland, ME.
9
Department of Neurology, Boston Children's Hospital, Boston, MA.
10
Department of Pathology, McGill University, Montreal Neurological Institute, Montreal, Canada.
11
Molecular Neurogenetics Unit, Institute for Research and Health Care (IRCCS) Foundation Carlo Besta Neurological Institute, Milan, Italy.
12
GeneDx, Gaithersburg, MD.
13
Kadlec Clinic Genetic Counseling, Richland, WA.
14
Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, WA.
15
Department of Pediatrics, Saint Justine University Hospital Center and University of Montreal, Montreal, Canada.
16
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.

Abstract

VPS13 protein family members VPS13A through VPS13C have been associated with various recessive movement disorders. We describe the first disease association of rare recessive VPS13D variants including frameshift, missense, and partial duplication mutations with a novel complex, hyperkinetic neurological disorder. The clinical features include developmental delay, a childhood onset movement disorder (chorea, dystonia, or tremor), and progressive spastic ataxia or paraparesis. Characteristic brain magnetic resonance imaging shows basal ganglia or diffuse white matter T2 hyperintensities as seen in Leigh syndrome and choreoacanthocytosis. Muscle biopsy in 1 case showed mitochondrial aggregates and lipidosis, suggesting mitochondrial dysfunction. These findings underline the importance of the VPS13 complex in neurological diseases and a possible role in mitochondrial function. Ann Neurol 2018;83:1089-1095.

PMID:
29518281
DOI:
10.1002/ana.25204
[Indexed for MEDLINE]

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