Primary familial brain calcification: Genetic analysis and clinical spectrum

• Published in: Movement disorders Vol. 29; no. 13; pp. 1691 - 1695
• Main Authors: Taglia, Ilaria, Mignarri, Andrea, Olgiati, Simone, Menci, Elisabetta, Petrocelli, Patrizia L., Breedveld, Guido J., Scaglione, Cesa, Martinelli, Paolo, Federico, Antonio, Bonifati, Vincenzo, Dotti, Maria Teresa
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2014; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Brain - diagnostic imaging; Brain - pathology; brain calcification; Brain Diseases - genetics; Brain Diseases - pathology; Brain Diseases - physiopathology; Calcinosis - genetics; Calcinosis - pathology; Calcinosis - physiopathology; Fahr's disease; Female; Genetic Testing; Humans; Male; Middle Aged; Movement disorders; Mutation - genetics; primary familial brain calcification; Radiography; SLC20A2; Sodium-Phosphate Cotransporter Proteins, Type III - genetics; Tomography Scanners, X-Ray Computed; primary familial brain calcification; brain calcification; SLC20A2; Fahr's disease
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26053

ABSTRACT 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. © 2014 International Parkinson and Movement Disorder Society