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TGFB1基因突变导致罕见进行性骨干发育不良

徐晓杰 马豆豆 吕芳 刘怡 王建一 姜艳 王鸥 夏维波 邢小平 李梅

徐晓杰, 马豆豆, 吕芳, 刘怡, 王建一, 姜艳, 王鸥, 夏维波, 邢小平, 李梅. TGFB1基因突变导致罕见进行性骨干发育不良[J]. 协和医学杂志, 2015, 6(5): 327-332. doi: 10.3969/j.issn.1674-9081.2015.05.003
引用本文: 徐晓杰, 马豆豆, 吕芳, 刘怡, 王建一, 姜艳, 王鸥, 夏维波, 邢小平, 李梅. TGFB1基因突变导致罕见进行性骨干发育不良[J]. 协和医学杂志, 2015, 6(5): 327-332. doi: 10.3969/j.issn.1674-9081.2015.05.003
Xiao-jie XU, Dou-dou MA, Fang Lü, Yi LIU, Jian-yi WANG, Yan JIANG, Ou WANG, Wei-bo XIA, Xiao-ping XING, Mei LI. Mutation in TGFB1 Causes Rare Progressive Diaphyseal Dysplasia[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(5): 327-332. doi: 10.3969/j.issn.1674-9081.2015.05.003
Citation: Xiao-jie XU, Dou-dou MA, Fang Lü, Yi LIU, Jian-yi WANG, Yan JIANG, Ou WANG, Wei-bo XIA, Xiao-ping XING, Mei LI. Mutation in TGFB1 Causes Rare Progressive Diaphyseal Dysplasia[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(5): 327-332. doi: 10.3969/j.issn.1674-9081.2015.05.003

TGFB1基因突变导致罕见进行性骨干发育不良

doi: 10.3969/j.issn.1674-9081.2015.05.003
基金项目: 

国家自然科学基金面上项目 8100623

国家临床重点专科建设项目 WBYZ2011-873

详细信息
    通讯作者:

    李梅 电话:010-69155088, E-mail:limeilzh@sina.com

  • 中图分类号: R681

Mutation in TGFB1 Causes Rare Progressive Diaphyseal Dysplasia

More Information
  • 摘要:   目的  分析1个进行性骨干发育不良(progressive diaphyseal dysplasia, PDD)家系患者的临床表型, 并检测转化生长因子β1编码基因TGFB1的突变类型。  方法  1例幼年起病, 表现为下肢骨痛、无力和肌肉减少的PDD患者, 来自非近亲婚配家庭, 评估其临床表现、骨骼X线特点、骨转换生化指标水平; 采用聚合酶链式反应及其产物直接Sanger测序法检测TGFB1突变。  结果  患者骨转换水平增高, 影像学提示患者四肢骨皮质不均匀性增厚、硬化。基因检测提示患者TGFB1基因第4外显子存在c.652C > T杂合性错义突变(p.Arg218Cys), 患儿父母均未发现该突变。予患者糖皮质激素治疗, 治疗4个月后患者骨痛缓解、活动能力明显改善。  结论  四肢骨痛和骨干皮质增厚是PDD的典型临床表现, TGFB1第218位点错义突变为PDD热点致病突变类型, 糖皮质激素治疗能够缓解PDD病情。
  • 图  1  进行性骨干发育不良患者家系图(A)及TGFB1基因测序结果(B)

    图  2  进行性骨干发育不良患者的影像学表现

    A.头颅侧位未见异常;B、E.治疗前患者股骨、胫腓骨骨干增粗,骨皮质不均匀增厚,骨小梁粗乱,相应骨髓腔变窄;C、D.治疗后患者股骨、胫腓骨表现未进一步加重

    图  3  进行性骨干发育不良TGFB1基因突变的DNA和蛋白位点

    UTR:非翻译区;LAP:潜活相关肽;TGFβ1:转化生长因子β1

    表  1  TGFB1基因PCR扩增引物序列

    外显子 引物名称 引物序列(5′→3′) 长度(bp) 退火温度(℃) 产物长度(bp)
    Exon 1 TGFB1-1F FCCCACGCGAGATGAGGAC 18 63 1464
    TGFB1-1R GCCAGTTTCTTCTGCCAGTC 20
    Exon 2 TGFB1-2F GAGACTGACTCCACCCCAGA 20 61 334
    TGFB1-2R TTGGTCACAGCTCACCCTCT 20
    Exon 3 TGFB1-3F GGTGGCTGTCTGAGAGGGTA 20 60 349
    TGFB1-3R GAGAGGGGTCCTAGGCAAAG 20
    Exon 4 TGFB1-4F GGTTTGCTCCTTCCTTCCTC 20 60 306
    TGFB1-4R AGTGAACCCTGCTTTGGTGT 20
    Exon 5 TGFB1-5F CGCCCCACTTATCTATCCCTC 21 60 379
    TGFB1-5R TCTTACACCCAGACCTCATCCC 22
    Exon 6 TGFB1-6F GGGCATGTGGCTTCTATGGTGG 22 58 276
    TGFB1-6R CCTCTTCCTCCGTCCTGGCTC 21
    Exon 7 TGFB1-7F GACAGGTGGGGAGAGACAGA 20 60 957
    TGFB1-7R CTGGTCTCAAATGCCTGGAT 20
    下载: 导出CSV

    表  2  进行性骨干发育不良患者治疗前后的临床特征

    时间 年龄(岁) 身高(cm) 体重(kg) Ca(mmol/L) P(mmol/L) ALP(U/L) β-CTX(ng/ml) 25OHD(nmol/L) PTH(ng/L) Cr(μmol/L) ALT(U/L) LS-BMD(g/cm2)* FN-BMD(g/cm2)* TH-BMD(g/cm2)*
    治疗前 7.1 118(-1SD) 16(-3SD) 2.31 1.49 200 1.20 23 8.7 31 13 0.673 (+1.2SD) 0.489(-2.3SD) 0.506
    治疗后2个月 7.2 118(-1SD) 21(-1SD) 2.47 1.37 193 0.47 46 13.7 28 18 - - -
    治疗后4个月 7.3 120(-1SD) 23(中位数) 2.50 1.53 185 0.84 / / 32 14 - - -
    SD:标准差;Ca:血钙;P:血磷;ALP:碱性磷酸酶;β-CTX:β胶原降解产物;25OHD:25羟维生素D;PTH:甲状旁腺素;Cr:肌酐;ALT:谷丙转氨酶;LS-BMD:腰椎骨密度;FN-BMD:股骨颈骨密度;TH-BMD:全髋骨密度;*由于目前治疗时间较短,治疗后骨密度尚未复查
    下载: 导出CSV
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出版历程
  • 收稿日期:  2015-07-18
  • 刊出日期:  2015-09-30

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