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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by a novel R782G mutation in CSF1R

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by a novel R782G mutation in CSF1R
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by a novel R782G mutation in CSF1R
We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum. The term "adult-onset leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease.
10042
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Hammans, Simon R.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Ellison, David W.
af9c60e1-3ac0-4bdc-96af-df910a7e9b79
Ditchfield, Adam
7af5f0f9-67d2-42c1-aae9-367e3b09946c
Beck, Sarah
188c036f-7fe7-444c-94b3-1760e4466dbf
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Hammans, Simon R.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Ellison, David W.
af9c60e1-3ac0-4bdc-96af-df910a7e9b79
Ditchfield, Adam
7af5f0f9-67d2-42c1-aae9-367e3b09946c
Beck, Sarah
188c036f-7fe7-444c-94b3-1760e4466dbf
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9

Foulds, Nicola, Pengelly, Reuben, Hammans, Simon R., Nicoll, James A.R., Ellison, David W., Ditchfield, Adam, Beck, Sarah and Ennis, Sarah (2015) Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by a novel R782G mutation in CSF1R. Scientific Reports, 5, 10042. (doi:10.1038/srep10042). (PMID:25975230)

Record type: Article

Abstract

We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum. The term "adult-onset leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease.

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Accepted/In Press date: 24 March 2015
Published date: 15 May 2015
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 377207
URI: https://eprints.soton.ac.uk/id/eprint/377207
PURE UUID: cdf7ac01-0419-491a-a120-9cb290cf6fc7
ORCID for Reuben Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869

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Date deposited: 28 May 2015 09:23
Last modified: 31 Jan 2019 01:37

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Contributors

Author: Nicola Foulds
Author: Reuben Pengelly ORCID iD
Author: Simon R. Hammans
Author: David W. Ellison
Author: Adam Ditchfield
Author: Sarah Beck
Author: Sarah Ennis ORCID iD

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