Gene Variants Related to Primary Familial Brain Calcification: Perspectives from Bibliometrics and Meta-Analysis

The genetic role and specific effects of primary familial cerebral calcification (PFBC) are still unclear. We aim to analyze bibliometric features in studies related to PFBC, investigate variant detection rates in patients with brain calcifications, and examine the phenotypic characteristics of PFBC patients. A comprehensive search of studies on the genetic effects of PFBC up until December 31, 2024, was conducted across Web of Science, PubMed, Embase, and Scopus. A random-effects meta-analysis combined variant detection rates for genes SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, JAM2, CMPK2, and NAA60 Data on total calcification scores (TCS), age of onset, and the prevalence of various phenotypes in PFBC patients were also aggregated. Publication bias was assessed using Egger's linear regression, and a leave-one-out sensitivity analysis was performed. Of 1,267 records, 224 were included in the bibliometric analysis. Keywords "primary familial brain calcification" and "SLC20A2" were most prominent. Eighteen articles were included in the meta-analysis, revealing higher variant rates for SLC20A2 (16.7%, 95% CI: 10.0-24.6) and MYORG (16.8%, 95% CI: 0.0-54.0), which were associated with higher TCS. The average age of onset was 43.69 years (95% CI: 36.17-51.21). Cognitive impairment (45.3%, 95% CI: 35.7-55.1) and psychiatric symptoms (30.8%, 95% CI: 17.2-46.2) had relatively higher prevalence rates. No significant publication bias was found (p > 0.05), and the sensitivity analysis confirmed the results' robustness. SLC20A2 and MYORG variants had higher detection rates, with cognitive impairment and psychiatric symptoms being common in PFBC patients. Continued research is essential to further explore these genetic variants.