Primary familial brain calcification: Genetic analysis and clinical spectrum
Ilaria Taglia1, Andrea Mignarri, Simone Olgiati
1Department of Medicine, Surgery and Neurosciences, University of Siena, Italy; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Background:
Primary familial brain calcification (PFBC) is a rare autosomal dominant disorder with bilateral calcification of basal ganglia and other cerebral regions, movement disorders, and neuropsychiatric disturbances. So far, three causative genes have been discovered: SLC20A2, PDGFRB and PDGFB, accounting for approximately 50% of cases.
Methods:
Seven unrelated families with primary brain calcification were recruited to undergo clinical and genetic analysis, including Sanger sequencing of SLC20A2, PDGFRB, and PDGFB, and copy number analysis of SLC20A2.
Results:
Mutations in SLC20A2 have been detected in three families: p.Glu368Glyfs*46, p.Ser434Trp, and p.Thr595Met. Intrafamilial phenotype variability has been observed. In spite of this, we found similar neuroimaging pattern among members of the same family.
Conclusions:
This molecular analysis expands the mutational spectrum of SLC20A2, which remains the major causative gene of primary familial brain calcification, and suggests the existence of disease-causing mutations in at least another, still unknown gene.
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