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A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder that typically presents with early-onset cognitive decline or personality change. The disease is associated with heterozygous mutations in the colony stimulating factor-1 receptor (CSF1R) gene....

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Autores principales: Yang, Xiaodong, Huang, Pei, Tan, Yuyan, Xiao, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541038/
https://www.ncbi.nlm.nih.gov/pubmed/31191609
http://dx.doi.org/10.3389/fgene.2019.00491
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author Yang, Xiaodong
Huang, Pei
Tan, Yuyan
Xiao, Qin
author_facet Yang, Xiaodong
Huang, Pei
Tan, Yuyan
Xiao, Qin
author_sort Yang, Xiaodong
collection PubMed
description Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder that typically presents with early-onset cognitive decline or personality change. The disease is associated with heterozygous mutations in the colony stimulating factor-1 receptor (CSF1R) gene. CSF1R activation regulates microglial survival, proliferation, and differentiation. The different gene mutations may be related to the various clinical phenotypes. Here, we described comprehensive clinical, neuroimaging, neuropathological, and genetic analyses of a family with HDLS. A novel splicing mutation in intron 13 (c.1858+1G>T) of CSF1R was found in this family. It is located at the splice site of intron 13, resulting in a splice donor site leading to exon 13 skipping from the CSF1R mRNA. The mother and two elderly siblings of the proband had the same CSF1R mutation as the proband but showed very mild neuroimaging abnormalities and mild memory loss, which did not affect daily life, indicating very uneven penetrance and distinctly different disease progression among family members. This report provides diverse neuroimaging and clinical characteristics of a novel CSF1R mutation with different disease penetrance. The large clinical heterogeneity in the same family who all had the same mutation indicates that modifying genes and environmental factors may play a role in the pathogenesis of HDLS.
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spelling pubmed-65410382019-06-12 A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids Yang, Xiaodong Huang, Pei Tan, Yuyan Xiao, Qin Front Genet Genetics Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder that typically presents with early-onset cognitive decline or personality change. The disease is associated with heterozygous mutations in the colony stimulating factor-1 receptor (CSF1R) gene. CSF1R activation regulates microglial survival, proliferation, and differentiation. The different gene mutations may be related to the various clinical phenotypes. Here, we described comprehensive clinical, neuroimaging, neuropathological, and genetic analyses of a family with HDLS. A novel splicing mutation in intron 13 (c.1858+1G>T) of CSF1R was found in this family. It is located at the splice site of intron 13, resulting in a splice donor site leading to exon 13 skipping from the CSF1R mRNA. The mother and two elderly siblings of the proband had the same CSF1R mutation as the proband but showed very mild neuroimaging abnormalities and mild memory loss, which did not affect daily life, indicating very uneven penetrance and distinctly different disease progression among family members. This report provides diverse neuroimaging and clinical characteristics of a novel CSF1R mutation with different disease penetrance. The large clinical heterogeneity in the same family who all had the same mutation indicates that modifying genes and environmental factors may play a role in the pathogenesis of HDLS. Frontiers Media S.A. 2019-05-22 /pmc/articles/PMC6541038/ /pubmed/31191609 http://dx.doi.org/10.3389/fgene.2019.00491 Text en Copyright © 2019 Yang, Huang, Tan and Xiao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yang, Xiaodong
Huang, Pei
Tan, Yuyan
Xiao, Qin
A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title_full A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title_fullStr A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title_full_unstemmed A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title_short A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
title_sort novel splicing mutation in the csf1r gene in a family with hereditary diffuse leukoencephalopathy with axonal spheroids
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541038/
https://www.ncbi.nlm.nih.gov/pubmed/31191609
http://dx.doi.org/10.3389/fgene.2019.00491
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