A Clinical And Genetic Study On Hereditary Diffuse Leukoencephalopathy With Spheroids(HDLS)

Purpose: Hereditary diffuse leukoencephalopathy with spheroids(HDLS)is an autosomal dominant hereditary leukodystrophy caused by CSF1 R gene mutation,which affect the tyrosine kinase domain.In this family with clinically misdiagnosed CADASIL,the clinical data,CSF1 R gene and m RNA expression were studied.Method: We collected detailed clinical data of proband and his families;we extracted peripheral blood of the proband and detected the common mutations in NOTCH3 gene;we sequenced the whole exon of patients with clinical symptoms and detected the expression of CSF1 R m RNA.Result: We did not detect the mutation of the NOTCH3 gene in the patients who had been misdiagnosed as CADASIL;the whole exon sequencing suggested that there was a splicing mutation in the sixteenth intron of the CSF1 R gene which is chr5:149436849 C > A;the expression of m RNA was significantly decrease;the mutation was found in the patients but not in normal populations.Conclusion: The clinical symptoms of HDLS are variable and HDLS was easily misdiagnosed as CADASIL or other diseases.Our study confirmed the splicing mutation as a pathogenic mutation by gene detection technique,which not only helped to make a clear diagnosis,but also expanded the gene spectrum of the disease.For patients with autosomal dominant hereditary white matter lesions,the possibility of HDLS disease cannot be ignored.