A novel SLC20A2 variant associated with primary brain calcification: A case report

A female patient in her late 50s was admitted with sudden-onset speech impairment. Brain computed tomography identified multiple intracranial calcifications alongside an acute ischemic lesion in the left frontoparietal region. Whole-genome sequencing revealed a novel frameshift variant in the SLC20A2 gene (c.1089del, p.Ile363MetfsTer92), which is associated with primary brain calcification. The variant was also detected in the patient's son and eldest daughter. Both of them demonstrated multiple intracranial calcifications on computed tomography, whereas the second daughter tested negative for the variant and showed no radiologic evidence of calcification. According to the American College of Medical Genetics and Genomics guidelines, the variant was classified as likely pathogenic. This case report documents a novel loss-of-function variant in SLC20A2 and expands the mutational spectrum of primary brain calcification. These findings highlight the clinical utility of genetic testing for diagnosis and genetic counseling in patients with primary brain calcification.