期刊
NEUROBIOLOGY OF AGING
卷 36, 期 2, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.09.005
关键词
Tauopathy; Seizures; Whole-exome sequencing; Synaptojanin
资金
- Government of Canada through the Genome Canada
- Canadian Institutes of Health Research (CIHR)
- Ontario Genomics Institute [OGI-049]
- Genome Quebec
- Genome British Columbia
- CIHR Institute of Genetics Clinical Investigatorship Award
- CIHR
The tauopathies are a heterogeneous group of neurodegenerative disorders characterized by the shared presence of tau aggregates and neurofibrillary tangles within the central nervous system. Here, we present a child with a severe neurodegenerative disorder characterized by intractable seizures and significant tau-immunoreactive neurofibrillary degeneration localized predominantly to the substantia nigra on neuropathology with absence of beta-amyloid plaques and Lewy or Pick bodies. Whole-exome sequencing identified a homozygous truncating mutation in Synaptojanin 1 (SYNJ1). Quantitative polymerase chain reaction and Western blot experiments demonstrated diminished SYNJ1 messenger RNA and protein. Knockout Synj1(-/-) mice have convulsions and die early in life. More recently, homozygous missense mutations have been reported in 2 families with early-onset parkinsonism and seizures. Our findings broaden the spectrum of disease associated with alteration of SYNJ1 and further implicate defects in synaptic vesicle recycling in the tauopathies. (C) 2015 Elsevier Inc. All rights reserved.
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