title: Novel mutations of PDGFRB cause primary familial brain calcification in Chinese families.
abstract: Four causative genes, including solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor b (PDGFRB), platelet-derived growth factor b (PDGFB)and xenotropic and polytropic retrovirus receptor 1 (XPR1), have been identified to cause primary familial brain calcification (PFBC). However, PDGFRB mutations seem to be quite rare and no PDGFRB mutations have been reported in Chinese PFBC patients. A total of 146 PFBC patients including 12 families and 134 sporadic patients were recruited in this study. All of them were previously tested negative for the SLC20A2. Mutational analyses of the entire exons and exon-intron boundaries of PDGFRB were carried out by direct gene sequencing. In silico analyses of the identified variants were conducted using Mutation Taster, PolyPhen-2 and Sorts Intolerant From Tolerant. Two heterozygous variants, c.3G>A and c.2209G>A, of the PDGFRB gene were revealed in two PFBC families, respectively. These two variants were not observed in 200 healthy controls. The variant c.3G>A was located in exon 2 and affected the initiation codon of the PDGFRB gene. The variant c.2209G>A resulted in amino-acid substitutions of aspartic acid to asparagine at position 737. Both of these two variants co-segregated with the disease phenotype (variant carriers in Family 1: I1, II2 and II3; variant carriers in Family 2: I2 and II8), suggesting a pathogenic impact of these variants. The prevalence of PDGFRB mutations in Chinese PFBC patients seems to be quite low, indicating that PDGFRB is not a major causative gene of PFBC in Chinese population.
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Yao
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Hai-Ting
authors.initials: HT
authors.lastname: Chen
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Lai
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Guo
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Su
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: En-Lin
authors.initials: EL
authors.lastname: Dong
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Qi-Jie
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.
authors.forename: Wan-Jin
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020574:Proto-Oncogene Proteins c-sis / Q000737:chemistry / Q000235:genetics*; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: D020574:Proto-Oncogene Proteins c-sis; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor