MYORG-associated primary brain calcification in Japan: A focus on consanguinity and brainstem calcification

Aims This study aimed to characterize the clinical features of MYORG -associated primary brain calcification (PBC) in Japan, with particular emphasis on consanguinity and marked brainstem calcification. Methods From a registry of 190 patients with PBC (93 males and 97 females) enrolled according to established diagnostic criteria, we identified patients with a history of consanguinity and those with marked brainstem calcification. Using samples from patients who had provided informed consent, we performed whole-exome sequencing by next-generation sequencing (NGS), followed by Sanger sequencing to confirm the identified variants. We then characterized the clinical features of patients harboring MYORG variants. Results Among 15 patients from consanguineous families, MYORG variants were identified in 6 of the 13 (46%) patients for whom genetic analysis was available, and all six exhibited marked brainstem calcification. In contrast, among seven non-consanguineous patients with marked brainstem calcification, a MYORG variant was identified in only one patient. Clinically, all seven patients with MYORG variants had dysarthria, which was the initial symptom in five patients. Four of the seven patients had also epilepsy. Conclusions MYORG variants were frequently identified among Japanese patients with PBC from consanguineous families. Consanguinity, marked brainstem calcification, and dysarthria appear to constitute three characteristic features of MYORG -associated PBC. Epilepsy may also be a relatively common clinical feature among Japanese patients with MYORG variants.