A novel A792D mutation in the CSF1R gene causes hereditary diffuse leukoencephalopathy with axonal spheroids characterized by slow progression

• Published in: eNeurologicalSci Vol. 1; no. 1; pp. 7 - 9
• Main Authors: Ueda, Sakiho, Yamashita, Hirofumi, Hikiami, Ryota, Sawamoto, Nobukatsu, Yoshida, Kunihiro, Takahashi, Ryosuke
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2015; Elsevier
• Subjects: A792D; Adult-onset cognitive impairment; Autosomal dominant; Case Report; CSF1R; HDLS; Hereditary diffuse leukoencephalopathy with spheroids; White matter disease; Autosomal dominant; CSF1R; HDLS; Adult-onset cognitive impairment; Hereditary diffuse leukoencephalopathy with spheroids; White matter disease; A792D
• ISSN: 2405-6502; 2405-6502
• DOI: 10.1016/j.ensci.2015.07.001

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant white matter disease that causes adult-onset cognitive impairment. The clinical manifestations are a variable combination of personality and behavioral changes, cognitive decline, parkinsonism, spasticity, and epilepsy. In 2012, mutations in the gene encoding colony stimulating factor 1 receptor (CSF1R) were identified as the cause of HDLS. As the numbers of reported mutations are limited, the understanding of whole pathogenesis needs accumulation of disease-causing mutations with detailed clinical descriptions. We describe a Japanese family with autosomal dominant adult-onset cognitive impairment and characteristic white matter lesions. Genetic testing revealed a novel p.A792D mutation in the tyrosine kinase domain of CSF1R in two affected family members. The symptom profile of the present cases mostly matched the previously reported cases, with the notable exceptions of late-onset and long disease duration. •We describe a Japanese family of hereditary diffuse leukoencephalopathy with spheroids (HDLS).•We identify a novel p.A792D mutation in the tyrosine kinase domain of CSF1R in two affected family members.•The present cases showed relatively slow-progressive courses.