The Genetics of Primary Familial Brain Calcification: A Literature Review.

1. Int J Mol Sci. 2023 Jun 29;24(13):10886. doi: 10.3390/ijms241310886. The Genetics of Primary Familial Brain Calcification: A Literature Review. Chen SY(1), Ho CJ(1), Lu YT(1), Lin CH(1), Lan MY(1)(2)(3), Tsai MH(1)(4)(5)(6). Author information: (1)Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan. (2)Center for Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan. (3)Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan. (4)School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan. (5)Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan. (6)Genomics and Proteomics Core Laboratory, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan. Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes (SLC20A2, PDGFRB, PDGFB, and XPR1) and three recessive inherited genes (MYORG, JAM2, and CMPK2). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies. DOI: 10.3390/ijms241310886 PMCID: PMC10342144 PMID: 37446066 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.