■CSF1R基因编码集落刺激因子-1的受体，即巨噬细胞，和单核细胞特异性生长因子。该基因的突变导致遗传性弥漫性白质脑病，伴有常染色体显性遗传的球状体（HDLS）和BANDDOS（脑异常，神经变性,和强肌硬化）具有常染色体隐性遗传。
■对死者患者的基因组DNA样本和胎儿及其家人的10名健康成员进行靶向基因测序，以鉴定致病突变。生物信息学工具用于研究突变对蛋白质功能和结构的影响。为了预测突变对蛋白质的影响，应用了各种生物信息学工具。
■在CSF1R基因中发现了一种新的纯合变体，c.2498C>T；p.T833M在第19外显子，在索引患者和胎儿中。此外，一些家族成员对这种变异是杂合的，虽然他们没有任何疾病的症状。计算机模拟分析表明该变体对CSF1R具有不利影响。它在人类和其他类似物种之间是保守的。该变体位于受体的功能性必需PTK结构域内。然而,这种替代没有引入结构损坏。
■总而言之，关于家庭中的遗传模式和索引患者的临床表现，我们认为CSF1R基因中提到的变异可能会导致BANDDOS。
UNASSIGNED: The CSF1R gene encodes the receptor for colony-stimulating factor-1, the macrophage, and monocyte-specific growth factor. Mutations in this gene cause hereditary diffuse leukoencephalopathy with spheroids (HDLS) with autosomal dominant inheritance and
BANDDOS (Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis) with autosomal recessive inheritance.
UNASSIGNED: Targeted gene sequencing was performed on the genomic DNA samples of the deceased patient and a fetus along with ten healthy members of his family to identify the disease-causing mutation. Bioinformatics tools were used to study the mutation effect on protein function and structure. To predict the effect of the mutation on the protein, various bioinformatics tools were applied.
UNASSIGNED: A novel homozygous variant was identified in the gene CSF1R, c.2498C>T; p.T833M in exon 19, in the index patient and the fetus. Furthermore, some family members were heterozygous for this variant, while they had not any symptoms of the disease. In silico analysis indicated this variant has a detrimental effect on CSF1R. It is conserved among humans and other similar species. The variant is located within the functionally essential PTK domain of the receptor. However, no structural damage was introduced by this substitution.
UNASSIGNED: In conclusion, regarding the inheritance pattern in the family and clinical manifestations in the index patient, we propose that the mentioned variant in the CSF1R gene may cause
BANDDOS.
PDF(Pubmed)