Background: Primary familial brain calcification (PFBC) is a rare hereditary neurodegenerative disorder associated with the MYORG gene; however, the clinical and radiological characteristics of MYORG-PFBC remain unclear.
Methods: We present relevant medical data obtained from a patient affected by PFBC with a novel MYORG variant and conducted a mutational analysis of MYORG in her family members. We reviewed all reported PFBC cases with biallelic MYORG mutations until April 1, 2023, and summarized the associated clinical and radiological features and mutation sites.
Results: The patient (22-year-old woman) exhibited paroxysmal limb stiffness and dysarthria for 3 years. Computed tomography revealed calcifications in the paraventricular white matter, basal ganglia, thalamus, and cerebellum. Whole-exome sequencing revealed a novel homozygous frameshift variant (c.743delG: p.G248Afs*32) in exon 2 of the MYORG gene (NM_020702.5). To date, 62 families and 64 mutation sites have been reported. Among the reported biallelic MYORG mutations, 57% were homozygous and 43% were compound heterozygous. Individuals with biallelic MYORG mutations experience more severe brain calcification with approximately 100% clinical penetrance. Ten single heterozygous mutation sites are associated with significant brain calcifications.
Conclusion: All patients with primary brain calcification, particularly younger patients without a family history of the disease, should be screened for MYORG mutations.
Keywords: Fahr's disease; MYORG gene; brain calcification; case report; homozygous mutation.
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.