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TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model  期刊论文  

  • 编号：
    d6dc442d-d8af-4f3f-9b7c-7b93b415b73e
  • 作者：
    Liu, Jiaqi[1,2,3,4,5];Wu, Nan[1,2,3,6,7];Yang, Nan[8,9,10];Takeda, Kazuki[11,12];Chen, Weisheng[1,2,13];Li, Weiyu[8,9];Du, Renqian[7];Sen Liu[1,2,3,6];Zhou, Yangzhong[2,3,14];Zhang, Ling[8,9];Liu, Zhenlei[3,15];Zuo, Yuzhi[1,2,3,6];Zhao, Sen[1,2,3];Blank, Robert[16];Pehlivan, Davut[7];Dong, Shuangshuang[8,9];Zhang, Jianguo[1,2,3,6];Shen, Jianxiong[1,2,3,6];Si, Nuo[2,17,18];Wang, Yipeng[1,2];Liu, Gang[1,2,3,6];Li, Shugang[1,2];Zhao, Yanxue[1,2,3];Zhao, Hong[1,2];Chen, Yixin[1,2,3];Zhao, Yu[1,2];Song, Xiaofei[7];Hu, Jianhua[1,2];Lin, Mao[1,2,3,13];Tian, Ye[1,2];Yuan, Bo[7];Yu, Keyi[1,2];Niu, Yuchen[2,3,19];Yu, Bin[1,2];Li, Xiaoxin[2,3,19];Chen, Jia[1,2,3];Yan, Zihui[1,2,3,13];Zhu, Qiankun[1,2,3];Meng, Xiaolu[2,17,18];Chen, Xiaoli[20];Su, Jianzhong[21];Zhao, Xiuli[2,17,18];Wang, Xiaoyue[2,18];Ming, Yue[5,22];Li, Xiao[2,23];Raggio, Cathleen L.[24];Zhang, Baozhong[1,2];Weng, Xisheng[1,2,3,6];Zhang, Shuyang[2,3,25];Zhang, Xue[2,3,17,18];Watanabe, Kota[12];Matsumoto, Morio[12];Jin, Li(金力)[8]Shen, Yiping[26,27];Sobreira, Nara L.[28];Posey, Jennifer E.[7];Giampietro, Philip F.[29];Valle, David[28];Liu, Pengfei[7,30];Wu, Zhihong[2,3,6,19];Ikegawa, Shiro[11];Lupski, James R.[7,31,32];Zhang, Feng[8,9,10];Qiu, Guixing[1,2,3,6];Kawakami, Noriaki;Kotani, Toshiaki;Sudo, Hideki;Yonezawa, Ikuho;Uno, Koki;Taneichi, Hiroshi;Watanabe, Kei;Minami, Shohei;Shigematsu, Hideki;Sugawara, Ryo;Taniguchi, Yuki;Ootomo, Nao;
  • 语种：
    英文
  • 期刊：
    GENETICS IN MEDICINE ISSN：1098-3600 2019 年 21 卷 7 期 (1548 - 1558) ; JUL
  • 收录：
     
  • 关键词：
    congenital scoliosis (CS) 16p11.2/TBX6 compound inheritance model genotype-phenotype correlation gene dosage
  • 摘要：

    Purpose: To characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model.
    Methods: Patients with congenital scoliosis (CS) from China (N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. A mouse model for Tbx6 compound inheritance (N= 52) was investigated by micro computed tomography (micro-CT). A clinical diagnostic algorithm (TACScore) was developed to assist in clinical recognition of TBX6-associated CS (TACS).
    Results: In cohort 1, TACS patients (N= 33) were significantly younger at onset than the remaining CS patients (P = 0.02), presented with one or more hemivertebrae/butterfly vertebrae (P = 4.9 x 10(-8)), and exhibited vertebral malformations involving the lower part of the spine (T8-S5, P = 4.4 x 10(-3)); observations were confirmed in two replication cohorts. Simple rib anomalies were prevalent in TAGS patients (P = 3.1 x 10(-7)), while intraspinal anomalies were uncommon (P = 7.0 x 10(-7)). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9 (P = 1.6 x 10(-15)). A Tbx6(-/mh (mild-hypomorphic)) mouse model supported that a gene dosage effect underlies the TACS phenotype.
    Conclusion: TACS is a clinically distinguishable entity with consistent clinically measurable endophenotypes. The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS.

  • 推荐引用方式
    GB/T 7714：
    Liu Jiaqi,Wu Nan,Yang Nan, et al. TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model [J].GENETICS IN MEDICINE,2019,21(7):1548-1558.
  • APA：
    Liu Jiaqi,Wu Nan,Yang Nan,Takeda Kazuki,&Ootomo Nao.(2019).TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model .GENETICS IN MEDICINE,21(7):1548-1558.
  • MLA：
    Liu Jiaqi, et al. "TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model" .GENETICS IN MEDICINE 21,7(2019):1548-1558.
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