Category: Parkinsonism (Other)
Objective: To update the genetic spectrum of primary familial brain calcification (PFBC) and phenotypic characteristics in genetically diagnosed PFBC, and provide genotype-imaging-symptoms correlations of PFBC.
Background: PFBC is a monogenic inherited disease characterized by calcifications in basal ganglia and other brain regions, with seven causative genes identified and highly heterogeneous genetic and phenotypic spectrum.
Method: 584 PFBC probands and 114 affected relatives were enrolled. Brain calcification was assessed by total calcification score (TCS). Sanger sequencing of SLC20A2 and whole-exome sequencing were performed. Variants was classified by ACMG Guidelines Revisions.
Results: 88 probands were genetically diagnosed with variants in SLC20A2 (75.86%), PDGFRB (2.30%), PDGFB (3.45%), XPR1(3.45%), MYORG (11.49%), JAM2 (3.45%), and NAA60 (1.15%). Totally, 29 unreported variants were detected. Age-adjusted analysis showed TCSs were significantly higher in autosomal recessive (AR) than in autosomal dominant (AD) (p < 0.005). AR-PFBC patients had higher rates with clinical symptoms than that in AD-PFBC (100.00% vs 55.06%, p < 0.001). In all PFBC, advancing age showed associations with headache/dizziness (OR = 0.97, p = 0.0241), cognitive dysfunction (OR = 1.07, p = 0.0025), and psychiatric symptoms (OR = 1.05, p = 0.0396). Regional calcification analysis revealed thalamic calcification scores were associated with cognitive impairment (OR = 1.34 p = 0.0026), followed by lenticular nucleus calcification with headache/dizziness (OR = 1.55, p = 0.0046), cerebellar hemisphere calcification with motor symptoms (OR = 1.45, p = 0.0051), and caudate nucleus calcification with psychiatric manifestations (OR = 1.2, p= 0.0351).
Conclusion: This large-scale Chinese cohort study demonstrates the genetic spectrum of PFBC and phenotypic characteristics in genetically diagnosed PFBC, and also provides genotype-imaging-symptoms correlations of PFBC.
To cite this abstract in AMA style:
ZD. Cen, ZR. Lin, W. Luo. The Genetic and Phenotypic Spectrum of Primary Familial Brain Calcification in a large cohort from China [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/the-genetic-and-phenotypic-spectrum-of-primary-familial-brain-calcification-in-a-large-cohort-from-china/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-genetic-and-phenotypic-spectrum-of-primary-familial-brain-calcification-in-a-large-cohort-from-china/