Highlights
- •We identified a novel CSF1R splice site mutation (c.2442 + 2T > C) in intron 18 in a Japanese family.
- •We detected atypical neuropathological findings in the frontal cortex and hippocampus, in addition to typical findings in HDLS.
- •Our results provide further evidence for the CSF1R mutation heterogeneity.
Abstract
Clinical phenotypes of hereditary diffuse leukoencephalopathy with spheroids (HDLS),
a familial progressive neurodegenerative disorder affecting the white matter of the
brain, are heterogenous and may include behavioral and personality changes, memory
impairment, parkinsonism, seizure, and spasticity. Thus, HDLS is frequently unrecognized
and misdiagnosed. Heterozygous mutations located within the kinase domain of the gene
encoding the colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor
with key roles in development and innate immunity, have been shown in HDLS. These
different gene mutations may be related to the various clinical phenotypes. We report
here a newly identified family with HDLS harboring a mutation in the CSF1R gene. We examined clinical and neuropathological features in three members of this
family. These patients presented with affective incontinence, memory impairment, and
executive dysfunction at onset, and revealed nonfluent aphasia, parkinsonism, and
seizure as the disease progressed. We identified a novel CSF1R splice site mutation (c.2442 + 2T > C) in intron 18 for two of the patients. MRI of these patients revealed progressive,
frontotemporal-predominant, confluent leukoencephalopathy. We also observed severe
myelin loss, axonal degeneration, and abundant axonal spheroids, astrocytes, and microglia
in the cerebral white matter, consistent with HDLS neuropathological features. Additionally,
we identified atypical neuropathological findings for HDLS, including neuronal loss
and gliosis with ballooned neurons and central chromatolysis in the frontal cortex
and hippocampus. This report provides further evidence for the clinical and neuropathological
heterogeneity of HDLS.
Keywords
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Article info
Publication history
Published online: June 07, 2016
Accepted:
June 6,
2016
Received in revised form:
May 17,
2016
Received:
December 30,
2015
Identification
Copyright
© 2016 Elsevier B.V. All rights reserved.
