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;
XU Xiao-jie;MA Dou-dou;Lü Fang;LIU Yi;WANG Jian-yi;JIANG Yan;WANG Ou;XIA Wei-bo;XING Xiao-ping;LI Mei;Department of Endocrinology,Key Laboratory of Endocrinology of Ministry of Health,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

• 1:中国医学科学院北京协和医学院北京协和医院内分泌科卫生部内分泌重点实验室

摘要(Abstract)：

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。
Objective To investigate the phenotypes of a kindred with progressive diaphyseal dysplasia( PDD) and to detect the mutation of transforming growth factor beta-1( TGFB1) gene. Methods A PDD patient of a non-consanguineous family presented with early onset in childhood,who suffered from lower limb pain,fatigability and muscle weakness. Her clinical manifestations,features of skeletal X-ray examination,and bone turnover markers were evaluated. Mutation of TGFB1 was identified by direct Sanger sequencing of polymerase chain reaction amplification product. Results The proband presented with elevated bone turnover biomarkers,and nonuniform thickening and sclerosis of bone cortex of limbs in X-ray films. A heterozygous missense mutation c. 652 C > T( p. Arg218Cys) in exon 4 of TGFB1 was identified in the proband,but not in either of her parents. Glucocorticoid was given and after 4 months of treatment,the bone pain and activity were obviously improved. Conclusions The typical clinical manifestations of PDD are limb pain and diaphyseal hyperostosis. The missense mutations at position 218 of TGFB1 are hotspot pathogenic mutations of PDD. Glucocorticoids can mitigate the symptoms in PDD patients.

关键词(KeyWords)： 进行性骨干发育不良;表现型;TGFB1基因;突变
progressive diaphyseal dysplasia;phenotype;TGFB1 gene;mutation

Abstract:

Keywords:

基金项目(Foundation): 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)

作者(Authors): 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;
XU Xiao-jie;MA Dou-dou;Lü Fang;LIU Yi;WANG Jian-yi;JIANG Yan;WANG Ou;XIA Wei-bo;XING Xiao-ping;LI Mei;Department of Endocrinology,Key Laboratory of Endocrinology of Ministry of Health,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

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