■CSF1R相关脑病是指由于CSF1R突变导致的具有神经轴突球状体和色素胶质细胞(ALSP)的成人发病脑白质营养不良,这是一种罕见的常染色体显性遗传白质疾病,包括两个病理实体,遗传性弥漫性脑白质病伴有球状体(HDLS)和色素性正色脑白质营养不良(POLD)。这项研究的目的是鉴定CSF1R基因中的其他致病突变并阐明其致病作用。
■根据2014年3月至2020年6月在宣武医院的临床和神经影像学检查结果,对9名被诊断为可能患有ALSP的中国患者进行了全外显子组测序(北京,中国)。根据美国医学遗传学和基因组学学会和分子病理学协会(ACMG/AMP)标准和指南评估变异体的致病性。
■9例患者发病年龄的平均值±标准差(范围)为39.22±9.63[25-54]岁。九个病人中有四个是男性,九个人中有四个有非凡的家族史。在9例患者中鉴定出7个CSF1R突变;4例(p。G17C,p.R579Q,p.I794Tandc.2909_2910insATCA)havebeenpreviouslyreported,而三(p。V613L,p.W821R和c.2442+2_2442+3dupT)是新颖的。在后者中,两个(p。V613L和p.W821R)可能具有致病性,根据ACMG/AMP标准,1(c.24422_24423dupT)具有不确定的意义。
■这些发现扩大了ALSP的突变谱,为今后对该病的病因和潜在治疗策略的研究提供了基础。
UNASSIGNED: CSF1R-related encephalopathy refers to adult-onset leukodystrophy with neuroaxonal spheroids and pigmented glia (ALSP) due to CSF1R mutations, which is a rare autosomal dominant white matter disease including two pathological entities, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). The aim of this study was to identify additional causative mutations in the CSF1R gene and clarify their pathogenic effects.
UNASSIGNED: Whole-exome sequencing was conducted for nine Chinese patients diagnosed with possible ALSP based on clinical and neuroimaging findings from March 2014 to June 2020 at Xuanwu Hospital (Beijing, China). Variant pathogenicity was assessed according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) Standards and Guidelines.
UNASSIGNED: Mean ± standard deviation (range) age of disease onset in the nine patients was 39.22±9.63 [25-54] years. Four of the nine patients were male, and four out of nine had a remarkable family history. Seven CSF1R mutations were identified in the nine patients; four (p.G17C, p.R579Q, p.I794T and c.2909_2910insATCA) have been previously reported, while three (p.V613L, p.W821R and c.2442+2_2442+3dupT) were novel. Of the latter, two (p.V613L and p.W821R) were likely pathogenic and 1 (c.2442+2_2442+3dupT) was of uncertain significance according to ACMG/AMP criteria.
UNASSIGNED: These findings expand the mutational spectrum of ALSP and provide a basis for future investigations on etiologic factors and potential management strategies for this disease.