First Japanese family with primary familial brain calcification due to a mutation in the PDGFB gene: an exome analysis study.

Abstract

Primary familial brain calcification (PFBC) is a rare disorder characterized by abnormal deposits of calcium in the basal ganglia and cerebellum. PFBC can present with a spectrum of neuropsychiatric symptoms resembling those seen in dementia and schizophrenia. Mutations in a few genes have been identified as causing PFBC: namely, the SLC20A2 gene that codes for the sodium-dependent phosphate transporter and the PDGFRB gene that codes for the platelet-derived growth factor receptor β (PDGF-Rβ). A recent study identified mutations in PDGFB coding for PDGF-B, the main ligand for PDGF-Rβ, in six families with PFBC. Here we report the first Japanese family with PFBC carrying a mutation in PDGFB, which causes the substitution of an arginine with a stop codon at amino acid 149 of the PDGF-B protein (p. Arg149*). Clinical histories and computed tomography scan images were provided. Sanger sequencing was performed for the exome analysis of SLC20A2 and PDGFB genes. One family member began to complain of auditory hallucination at 16 years of age and had been treated for schizophrenia. His father suffered from memory and gait disturbances in his late 60s. A computed tomography scan revealed a symmetrical area of calcification over the basal ganglia in both cases. A known mutation in PDGFB (c.445C>T, p.Arg149*) was consistently detected in both PFBC cases by Sanger sequencing. No mutations in SLC20A2 were detected. Our findings suggest that this mutation in PDGF-B is responsible for PFBC in this Japanese family and that abnormal PDGF signaling may be involved in the pathophysiology of certain psychiatric disorders.