Foulds Nicola, Pengelly Reuben J, Hammans Simon R, Nicoll James A R, Ellison David W, Ditchfield Adam, Beck Sarah, Ennis Sarah
1] Wessex Clinical Genetics Services, University Hospital Southampton NHS Foundation Trust, UK [2] Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, UK. Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, UK.
Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, UK. Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, UK.
Sci Rep. 2015 May 15;5:10042. doi: 10.1038/srep10042.
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.
我们报告了一个新的家族，其常染色体显性遗传一种迟发性快速进展性脑白质营养不良，外显子组测序在集落刺激因子1受体基因（CSF1R）中发现了一个新的p.R782G突变。两名患病家族成员的神经病理学检查显示脑白质变性伴轴突肿胀和色素性巨噬细胞。最近报道的少数携带CSF1R突变的家族之前被标记为“伴有轴突球体的遗传性弥漫性脑白质病”（HDLS）和“色素性正染性脑白质营养不良”（POLD），现在看来这些疾病构成了一个疾病连续体。有人提出用“成人起病的伴有轴突球体和色素性神经胶质细胞的脑白质病”（ALSP）这一术语来涵盖这一谱系。由于CSF1R调节小胶质细胞，这种突变意味着小胶质细胞的失调是该疾病的主要病因。
