CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.

Abstract

Mutations in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hereditary diffuse leukoencephalopathy with axonal spheroids. We identified a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.(E664K)] by exome sequencing in five members of a family with hereditary diffuse leukoencephalopathy with axonal spheroids. Three affected siblings had characteristic white matter abnormalities and presented with progressive neurological decline. In the fourth affected sibling, early progression halted after allogeneic haematopoietic stem cell transplantation from a related donor. Blood spot DNA from this subject displayed chimerism in CSF1R acquired after haematopoietic stem cell transplantation. Interestingly, both parents were unaffected but the mother's blood and saliva were mosaic for the CSF1R mutation. Our findings suggest that expression of wild-type CSF1R in some cells, whether achieved by mosaicism or chimerism, may confer benefit in hereditary diffuse leukoencephalopathy with axonal spheroids and suggest that haematopoietic stem cell transplantation might have a therapeutic role for this disorder.

• Authors: Florian S Eichler, Jiankang Li, Yiran Guo, Paul A Caruso, Andrew C Bjonnes, Jessica Pan, Jessica K Booker, Jacqueline M Lane, Archana Tare, Irma Vlasac, Hakon Hakonarson, James F Gusella, Jianguo Zhang, Brendan J Keating, Richa Saxena
• Journal: Brain : a journal of neurology (Brain) Vol. 139 Issue Pt 6 Pg. 1666-72 (06 2016) ISSN: 1460-2156 [Electronic] England
• PMID: 27190017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Receptor, Macrophage Colony-Stimulating Factor

Topics

• Adult
• Aged, 80 and over
• Chimerism
• Female
• Genetic Predisposition to Disease (genetics)
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukoencephalopathies (genetics, surgery)
• Male
• Middle Aged
• Mosaicism
• Mutation, Missense
• Receptor, Macrophage Colony-Stimulating Factor (genetics)