title: Mutation screening of PDGFB gene in Chinese population with primary familial brain calcification.
abstract: BACKGROUND
  Until recently, primary familial brain calcification (PFBC) has been determined by four genes, SLC20A2, PDGFRB, PDGFB and XPR1. No studies have been carried out to analyze the gene mutation of PDGFB in Chinese population.
  
  
  OBJECTIVE
  To screen mutations of PDGFB gene in a large cohort of Chinese PFBC patients with no SLC20A2 mutations.
  
  
  METHODS
  We recruited 192 PFBC patients, including 21 index cases and 171 sporadic cases, in our study. Peripheral venous blood samples of all included participants were collected for genomic DNA extraction. The coding sequence of PDGFB was amplified by polymerase chain reaction (PCR) followed by direct sequencing. The potential effects of the identified variants on protein function were assessed by bioinformatics analysis.
  
  
  RESULTS
  Three missense variants (c.35G>T, c.232C>T, and c.610C>A) and one nonsense variant (c.220G>T) of PDGFB were identified in five sporadic PFBC patients. The variant c.35G>T was found in 2 healthy controls from the same ethnic background, whereas c.220G>T, c.232C>T and c.610C>A were absent from 500 controls. c.220G>T (p.E74*) produced a stop codon in the place of the glutamicacid residue number 74. c.232C>T (p.R78C) occurred at highly conserved regions and were predicted as damaging by at least two computational predictive programs, suggesting that this variant were likely to have a causal role in PFBC. Although variant c.610C>A (p.P204T) also occurred at a highly conserved region, it was predicted to be most likely benign by two computational predictive programs, suggesting an uncertain role of this variant on PFBC.
  
  
  CONCLUSIONS
  The present study identified one likely pathogenic variant (p.E74*) and two variants of uncertain significance (p.R78C and p.P204T) in PDGFB. Further studies of PDGF-B functional expression for these variants are still required to confirm the pathogenic effect.
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Yao
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Chong-
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Su
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Guo
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Lu
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Yao-Bin
authors.initials: YB
authors.lastname: Liu
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Lai
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Hai-Ting
authors.initials: HT
authors.lastname: Chen
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fuzhou, China. Electronic address: wanjinchen75@fjmu.edu.cn.
authors.forename: Wan-Jin
authors.initials: WJ
authors.lastname: Chen
keywords: Idiopathic basal ganglia calcification; Mutations; PDGFB; Primary familial brain calcification