Novel mutations of PDGFRB cause primary familial brain calcification in Chinese families
Novel mutations of PDGFRB cause primary familial brain calcification in Chinese families
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PDGFRB新突变导致中国家庭原发性家族性脑钙化
DOI：
10.1038/jhg.2017.25
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发表时间：
2017-03
影响因子：
3.5
通讯作者：
Chen Wan-Jin
中科院分区：
文献类型：
--
作者：
Wang Chong;Yao Xiang-Ping;Chen Hai-Ting;Lai Jing-Hui;Guo Xin-Xin;Su Hui-Zhen;Dong En-Lin;Zhang Qi-Jie;Wang Ning;Chen Wan-Jin
目前已发现4个致病基因，包括溶质载体家族20成员2（SLC 20 A2）、血小板衍生生长因子受体B（PDGFR B）、血小板衍生生长因子B（PDGFB）和异嗜性和多嗜性逆转录病毒受体1（XPR 1），可引起原发性家族性脑钙化（PFBC）。然而，PDGFRB突变似乎是相当罕见的，在中国PFBC患者中没有PDGFRB突变的报道。本研究共收集了146例PFBC患者，包括12个家族和134例散发患者。所有这些人先前对SLC 20 A2的检测均为阴性。通过直接基因测序对PDGFRB的整个外显子和外显子-内含子边界进行突变分析。使用Mutation Taster、PolyPhen-2和不耐受与耐受分类对已鉴定变体进行计算机模拟分析。两个杂合子变体，c. 3G> A和C。2209 G> A的突变。在200名健康对照者中未观察到这两种变异。变种C 3G> A位于PDGFRB基因第2外显子，影响PDGFRB基因的起始密码子。变种C 2209 G> A导致737位天冬氨酸被天冬酰胺取代。这两种变异都与疾病表型共分离（家族1中的变异携带者：I1、II 2和II 3;家族2中的变异携带者：I2和II 8），表明这些变异具有致病性影响。PDGFRB基因突变在中国人群中的发生率较低，提示PDGFRB基因不是中国人群中PFBC的主要致病基因。
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.
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影响因子：
3.7
作者：
Vanlandewijck M;Lebouvier T;Andaloussi Mäe M;Nahar K;Hornemann S;Kenkel D;Cunha SI;Lennartsson J;Boss A;Heldin CH;Keller A;Betsholtz C
通讯作者：
Betsholtz C
影响因子：
5.3
作者：
Arts FA;Velghe AI;Stevens M;Renauld JC;Essaghir A;Demoulin JB
通讯作者：
Demoulin JB
影响因子：
10.5
作者：
M. Tallquist;R. Klinghoffer;R. Heuchel;P. F. Mueting-Nelsen;P. Corrin;C. Heldin;R. Johnson;Philippe Sor
通讯作者：
M. Tallquist;R. Klinghoffer;R. Heuchel;P. F. Mueting-Nelsen;P. Corrin;C. Heldin;R. Johnson;Philippe Sor
影响因子：
30.8
作者：
Keller, Annika;Westenberger, Ana;Oliveira, Joao R. M.
通讯作者：
Oliveira, Joao R. M.
影响因子：
14.5
作者：
Nicolas, Gael;Pottier, Cyril;Hannequin, Didier
通讯作者：
Hannequin, Didier