Eichler Florian S, Li Jiankang, Guo Yiran, Caruso Paul A, Bjonnes Andrew C, Pan Jessica, Booker Jessica K, Lane Jacqueline M, Tare Archana, Vlasac Irma, Hakonarson Hakon, Gusella James F, Zhang Jianguo, Keating Brendan J, Saxena Richa
1 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA 2 Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA 3 Center for Rare Neurological Diseases, Massachusetts General Hospital, Boston, MA, 02114, USA
4 BGI-Shenzhen, Shenzen 518083, China 5 Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen 518083, China.
Brain. 2016 Jun;139(Pt 6):1666-72. doi: 10.1093/brain/aww066. Epub 2016 May 5.
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.
集落刺激因子1受体（CSF1R）突变最近被发现是遗传性弥漫性白质脑病伴轴突球状体的病因。我们通过外显子组测序在一个患有遗传性弥漫性白质脑病伴轴突球状体的家族的五名成员中，鉴定出CSF1R中的一个新的杂合错义突变[c.1990G > A p.(E664K)]。三名受影响的兄弟姐妹有特征性的白质异常，并出现进行性神经功能衰退。在第四名受影响的兄弟姐妹中，在接受来自相关供体的异基因造血干细胞移植后，早期病情进展停止。该受试者的血斑DNA显示在造血干细胞移植后获得的CSF1R中存在嵌合现象。有趣的是，父母双方均未受影响，但母亲的血液和唾液中存在CSF1R突变的嵌合体。我们的研究结果表明，在某些细胞中野生型CSF1R的表达，无论是通过嵌合体还是嵌合现象实现，可能会在遗传性弥漫性白质脑病伴轴突球状体中带来益处，并表明造血干细胞移植可能对这种疾病具有治疗作用。
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