Abstract
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 brain calcification scores, 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 scores. 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.
Significance Statement This study reveals that SLC20A2 and MYORG gene variants are key drivers of primary familial brain calcification (PFBC), a neurodegenerative disorder marked by brain calcium deposits. Using global data, we show these variants correlate with severe calcification and frequently manifest as cognitive decline or psychiatric symptoms, while nearly a quarter of patients remain asymptomatic. By integrating genetic and clinical analyses, we provide the first systematic comparison of PFBC-associated genes and phenotypes, offering critical insights for diagnosis, genetic counseling, and mechanistic research. These findings highlight the need for expanded screening of understudied genes and global collaborations to address gaps in understanding this underdiagnosed condition, ultimately guiding therapeutic strategies for affected individuals.
Footnotes
We would like to express our gratitude to the developers of the bibliometrix package, Massimo Aria and Corrado Cuccurullo, for providing a comprehensive and flexible tool for science mapping analysis. We appreciate their efforts and contributions to the bibliometric community.
All authors declare that they have no conflicts of interest.
↵§Co-first author: Dehao Yang, Yangguang Lu and Honghao Huang
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
