文献类型：期刊文献

英文题名：Underestimated disease prevalence and severe phenotypes in patients with biallelic variants: A cohort study of primary familial brain calcification from China

作者：Chen, Si[1,2];Cen, Zhidong[1,2];Fu, Feng[1,3];Chen, You[1,2];Chen, Xinhui[4];Yang, Dehao[1,2];Wang, Haotian[1];Wu, Hongwei[5];Zheng, Xiaosheng[6];Xie, Fei[7];Ouyang, Zhiyuan[1];Tang, Weiguo[8];Zhang, Shuhong[9];Yin, Lili[10];Zhang, Yunqian[11];Meng, Peiying[12];Zhu, Xuzhen[13];Zhang, Hongwei[14];Jiang, Feifei[15];Zhang, Kaiyu[16];He, Juping[17];Zhang, Danhong[18];Ming, Hanqiao[19];Song, Daqiao[20];Zho, Zhiping[21];Luo, Yong[22];Gu, Qun[23];Su, Yongkun[24];Wu, Xinxiao[25];Tang, Haiyan[26];Wu, Chenglong[27];Chen, Weiqing[28];Liu, Jing-Yu[29];Luo, Wei[1];Huang, Xuerong[30];Fu, Shaowei[31];Chen, Wenhai[32];Huang, Yanbin[33];Lan, Likang[34];Zhu, Xiaofen[35];Xu, Zhijun[36];Huang, Huayun[37];Zhou, Lifeng[38];Chen, Zilong[39];Lou, Minfang[40];Wang, Binglan[41];Tan, Yi[42];Zhu, Manlian[43];Hong, Weijun[44];Wang, Feng[45];Pan, Gonghua[46];Shao, Aimin[47];Li, Weiying[48];Li, Haijun[49];Zhao, Na[50];Hu, Haoyu[51];Zhang, Yaxi[52];Lian, Mengjia[53];Li, Jieying[54];Cai, Xueli[55];Luo, Zixian[56];Zhou, Yan[57];Lu, Xiaoyi[58];Ma, Li[59];Xia, Enkui[60];Zhang, Xiaoluo[61]

机构：[1]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou 310009, Zhejiang, Peoples R China;[2]Zhejiang Univ, Key Lab Canc Prevent & Intervent, Affiliated Hosp 2, Sch Med,Canc Inst,China Natl Minist Educ, Hangzhou, Zhejiang, Peoples R China;[3]Zhuji Peoples Hosp Zhejiang Prov, Dept Neurol, Shaoxing, Zhejiang, Peoples R China;[4]Zhejiang Univ, Chu Kochen Honors Coll, Hangzhou, Zhejiang, Peoples R China;[5]Lishui Peoples Hosp, Dept Neurol, Lishui, Zhejiang, Peoples R China;[6]Zhejiang Hosp, Dept Intens Care Unit, Hangzhou, Zhejiang, Peoples R China;[7]Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Neurol, Hangzhou, Zhejiang, Peoples R China;[8]Zhoushan Hosp, Dept Neurol, Zhoushan, Zhejiang, Peoples R China;[9]Longyou Peoples Hosp, Dept Neurol, Quzhou, Zhejiang, Peoples R China;[10]Sanmen Peoples Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[11]Kunming Med Univ, Affiliated Hosp 4, Dept Neurol, Kunming, Yunnan, Peoples R China;[12]Zhuji Cent Hosp, Dept Neurol, Shaoxing, Zhejiang, Peoples R China;[13]Hangzhou Hosp Tradit Chinese Med, Dept Neurol, Hangzhou, Zhejiang, Peoples R China;[14]Shaoxing Univ, Affiliated Hosp, Deportment Neurol, Shaoxing, Zhejiang, Peoples R China;[15]Quzhou Peoples Hosp, Dept Neurol, Quzhou, Zhejiang, Peoples R China;[16]Huangyan Dist Hosp Tradit Chinese Med, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[17]Dongyang Peoples Hosp, Dept Neurol, Jinhua, Zhejiang, Peoples R China;[18]Taizhou Cent Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[19]Jiangshan Peoples Hosp, Dept Neurol, Quzhuo, Zhejiang, Peoples R China;[20]Yiwu Hosp Tradit Chinese Med, Dept Neurol, Jinhua, Zhejiang, Peoples R China;[21]Taishun Peoples Hosp, Dept Neurol, Wenzhou, Zhejiang, Peoples R China;[22]Jinhua Municipal Cent Hosp, Dept Neurol, Jinhua, Zhejiang, Peoples R China;[23]Huzhou First Peoples Hosp, Dept Neurol, Huzhou, Zhejiang, Peoples R China;[24]Tianzhu Peoples Hosp Qiandongnan Miao & Dong Auto, Dept Neurol, Guiyang, Guizhou, Peoples R China;[25]Qingyuan Peoples Hosp, Dept Neurol, Lishui, Zhejiang, Peoples R China;[26]Huzhou Cent Hosp, Dept Neurol, Huzhou, Zhejiang, Peoples R China;[27]Shaoxing Peoples Hosp, Dept Neurol, Shaoxing, Zhejiang, Peoples R China;[28]Xianju Peoples Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[29]Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China;[30]Wenzhou Med Univ, Affiliated Hosp 3, Dept Neurol, Wenzhou, Zhejiang, Peoples R China;[31]Peoples Hosp Suichang Cty, Dept Neurol, Lishui, Zhejiang, Peoples R China;[32]Li Ping Peoples Hosp, Dept Neurol, Guiyang, Guizhou, Peoples R China;[33]Yueqing Peoples Hosp, Dept Neurol, Wenhzou, Zhejiang, Peoples R China;[34]Lishui Peoples Hosp, Dept Neurol, Lishui, Zhejiang, Peoples R China;[35]Quzhou Kecheng Peoples Hosp, Dept Neurol, Quzhou, Zhejiang, Peoples R China;[36]Changshan Hosp Tradit Chinese Med, Dept Neurol, Changshan, Zhejiang, Peoples R China;[37]Changxing Cty Peoples Hosp, Dept Neurol, Huzhou, Zhejiang, Peoples R China;[38]Lishui Hosp Tradit Chinese Med, Dept Neurol, Lishui, Zhejiang, Peoples R China;[39]Yiwu Cent Hosp, Dept Neurol, Yiwu, Zhejiang, Peoples R China;[40]Quzhou Municipal Hosp Tradit Chinese Med, Dept Neurol, Quzhou, Zhejiang, Peoples R China;[41]Longquan Peoples Hosp, Dept Neurol, Lishui, Zhejiang, Peoples R China;[42]Quhua Hosp ZheJiang, Dept Neurol, Quzhou, Zhejiang, Peoples R China;[43]Second Peoples Hosp Lishui, Dept Neurol, Lishui, Zhejiang, Peoples R China;[44]Enze Hosp, Taizhou Enze Med Ctr Grp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[45]Taizhou Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[46]Yuhuan 2 Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[47]First Peoples Hosp Linhai, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[48]Taizhou First Peoples Hosp, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[49]Taizhou Municipal Hosp Zhejiang Prov, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[50]Zhejiang Chinese Med Univ, Wenzhou Hosp Tradit Chinese Med, Dept Neurol, Wenzhou, Zhejiang, Peoples R China;[51]Zhejiang Jinhua Hosp Tradit Chinese Med, Dept Neurol, Jinhua, Zhejiang, Peoples R China;[52]Wenzhou Cent Hosp, Dept Neurol, Wenzhou, Zhejiang, Peoples R China;[53]First Peoples Hosp Wenling, Dept Neurol, Taizhou, Zhejiang, Peoples R China;[54]Guiyang Second Peoples Hosp, Dept Neurol, Guiyang, Guizhou, Peoples R China;[55]Lishui Municipal Cent Hosp, Dept Neurol, Lishui, Zhejiang, Peoples R China;[56]First Peoples Hosp Yongkang, Dept Neurol, Jinhua, Zhejiang, Peoples R China;[57]Zhuji Hosp Tradit Chinese Med, Dept Neurol, Shaoxing, Zhejiang, Peoples R China;[58]Wenzhou Med Univ, Affiliated Hosp 2, Dept Neurol, Wenzhou, Zhejiang, Peoples R China;[59]Shaoxing Second Peoples Hosp, Dept Neurol, Shaoxing, Zhejiang, Peoples R China;[60]Zhe Jiang Putuo Hosp, Dept Neurol, Zhoushan, Zhejiang, Peoples R China;[61]Wenling Hosp Tradit Chinese Med, Dept Neurol, Taizhou, Zhejiang, Peoples R China

年份：2019

卷号：64

起止页码：211

外文期刊名：PARKINSONISM & RELATED DISORDERS

收录：SCI-EXPANDED(收录号：WOS:000487567800031)、、Scopus(收录号：2-s2.0-85064241338)、WOS

基金：This study was supported by the National Natural Science Foundation of China (Proj. No. 81870895, No. 81600850, No. 81571089, No. 81371266, No. 31671301, and No. 31871262), the Science Technology Department of Zhejiang Province (2019C03017), the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2018KY176), and the National Key Research and Development Program of China (2016YFC1306000).

语种：英文

外文关键词：Primary familial brain calcification; Estimated minimal prevalence; Biallelic variants

外文摘要：Background: Primary familial brain calcification (PFBC) is a rare calcifying disorder of the brain with extensive clinical and genetic heterogeneity. Its prevalence is underestimated due to clinical selection bias (compared with symptomatic PFBC patients, asymptomatic ones are less likely to undergo genetic testing). Methods: A total of 273 PFBC probands were enrolled in a multicenter retrospective cohort study by two different approaches. In Group I (nonsystematic approach), 37 probands diagnosed at our clinic were enrolled. In Group II (systematic approach), 236 probands were enrolled by searching the medical imaging databases of 50 other hospitals using specific keywords. Genetic testing of four genes known to be causative of autosomal dominant PFBC was performed in all probands using cDNA. All identified variants were further confirmed using genomic DNA and classified according to ACMG-AMP recommendations. Results: Thirty-two variants including 22 novel variants were detected in 37 probands. Among these probands, 83.8% (31/37) were asymptomatic. Two probands with homozygous pathogenic SLC20A2 variants presented more severe brain calcification and symptoms. Based on the variant detection rate of probands in Group II, we extrapolated an overall minimal prevalence of PFBC of 6.6 per 1,000, much higher than previously reported (2.1 per 1000). Conclusions: We identified a higher proportion of genetically confirmed PFBC probands who were asymptomatic. These patients would be overlooked due to clinical selection bias, leading to underestimation of the disease prevalence. Considering that PFBC patients with biallelic variants had more severe phenotypes, this specific condition should be focused on in genetic counseling.