The first Japanese case of primary familial brain calcification caused by an MYORG variant

• Published in: Journal of human genetics Vol. 65; no. 10; pp. 917 - 920
• Main Authors: Kume, Kodai, Takata, Tadayuki, Morino, Hiroyuki, Matsuda, Yukiko, Ohsawa, Ryosuke, Tada, Yui, Kurashige, Takashi, Kawakami, Hideshi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2020
• Subjects: Adult; Amino Acid Substitution; Asian Continental Ancestry Group - genetics; Basal ganglia; Brain Diseases - diagnostic imaging; Brain Diseases - genetics; Brain Diseases - pathology; Brain stem; Calcification; Calcification (ectopic); Calcinosis - diagnostic imaging; Calcinosis - genetics; Calcinosis - pathology; Cerebellar ataxia; Cerebellar Ataxia - genetics; Cerebellum; Computed tomography; Consanguinity; Dysarthria; Dysarthria - genetics; Female; Glycoside Hydrolases - chemistry; Glycoside Hydrolases - genetics; Headache; Headache - genetics; Homozygote; Humans; Japan; Mutation, Missense; Neuroimaging; Pedigree; Point Mutation; Pons; Substantia alba; Whole Exome Sequencing; Japan
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-020-0779-x

Primary familial brain calcification (PFBC) is a hereditary neurological disorder characterized by idiopathic calcification of the bilateral basal ganglia and other areas of the brain. MYORG has been identified as the first causative gene of autosomal recessive PFBC in Chinese families. There have been several reports of PFBC associated with MYORG (MYORG-PFBC) in individuals of Middle Eastern, European, and Latin American ancestry but to date, there have been no reported Japanese cases. We report the first Japanese case of MYORG-PFBC. The patient was a 43-year-old Japanese woman who experienced mild headaches and cerebellar ataxia including dysarthria. Computed tomography showed calcification in the cerebral white matter, basal ganglia, cerebellum, and brainstem. Using exome sequencing, we identified a homozygous variant in the MYORG gene (NM_020702.4: c.794C>T,p.Thr265Met). Our patient presented dysarthria and extensive calcification affecting the pons, which are specific features of MYORG-PFBC. We report clinical symptoms and imaging findings of a case with p.Thr265Met variant.