一个遗传性弥漫性脑白质病变合并球状轴索家系的CSFIR基因突变分析

Analysis of CSF1R gene mutation in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids

目的探讨1个常染色体显性遗传的弥漫性脑白质病变合并球状轴索（hereditary diffuse leukoencephalopathy with neuroaxonal spheroids，HDLs）家系的临床和影像学特点并进行CSF1R基因突变分析，为家系提供遗传咨询和产前诊断。方法根据先证者家族史、临床体征、头颅磁共振进行临床诊断；收集先证者及其家系成员外周血，常规提取基因组DNA；应用聚合酶链反应及DNA直接测序的方法进行集落刺激因子1受体（colony stimulating factor 1 receptor，CSFIR）基因的突变检测，分析基因型与表型的关系。结果该家系为典型的HDLS家系，5代34人共有9例受里成员，现存患者5例（其中1例在随访过程中死亡）。DNA测序结果显示，先证者存在CSF1R基因第20外显子c．2563C〉A（p．P855T）错义突变，在4名家系成员中也检测到该错义突变，其中3例出现临床症状，1例为无症状携带者。结论该HDLS家系符合常染色体显性遗传，为CSF1R基因c．2563C〉A（p．P855T）突变所致。

Objective To identify potential mutation of the colony stimulating factor I receptor gene fCSFIR） in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids （HDLS） and analyze the genotype-phenotype correlation. Methods The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing. Results There were 9 affected members （5 alive） in this five-generation family （1 member had died during the follow-up）. A missense mutation c. 2563C〉A （p. P855T） of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family. Conclusion The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.