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进行性骨干发育不良症临床特点及致病基因突变1例家系研究 预览

Investigation of clinical features and pathogenic gene mutation in a family with progressive diaphyseal dysplasia
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摘要 目的分析进行性骨干发育不良症(progressive diaphyseal dysplasia,PDD)临床特点和致病基因TGFB1的突变类型。方法纳入1例自幼起病男童,主要表现为步态摇摆,采集患儿病史,测量骨骼相关生化指标及骨密度,完善骨骼影像学检查。采用直接Sanger测序法检测患儿及其父母TGFB1基因突变。结果患儿血清Ⅰ型胶原C端肽β降解产物(β-C-terminal telopeptide of typeⅠcollagen,β-CTX)水平升高,碱性磷酸酶水平正常,骨密度显著降低(股骨颈0.406 g/cm~2,Z值-3.9;腰椎2-4 0.490 g/cm~2,Z值-0.4)。骨骼X线片提示患儿四肢长骨骨皮质局部增厚、硬化,骨小梁粗乱,骨髓腔狭窄,颅底及骨盆局部骨质增厚、硬化。基因检测提示患儿存在TGFB1第4外显子c.652C〉T(p.R218C)杂合错义突变,父母均未发现携带该突变。给予患儿糖皮质激素治疗,目前随访观察中。结论骨转换增快,骨皮质局部增厚、硬化,骨小梁粗乱,相应髓腔狭窄是PDD的典型临床特点。TGFB1基因c.652C〉T(p.R218C)突变是PDD致病原因之一。对PDD表型及致病分子机制的研究,有助于加深对此罕见骨骼疾病的认识。 Objective To investigate the clinical features and TGFB1 gene mutation in a family with progressive diaphyseal dysplasia( PDD). Methods We included a 2 years and 11 months old boy with gait swing as main manifestation. The medical history,biochemical markers,bone mineral density( BMD),and bone image were investigated. We identified the TGFB1 gene mutation by direct Sanger sequencing of polymerase chain reaction amplification product in the patient and his parents. Results The proband manifested as high serum level of β-C-terminal telopeptide of type Ⅰ collagen( β-CTX),normal ALP,low bone mineral density( BMD at femoral neck: 0. 406 g/cm~2,Z score:-3. 9,BMD at lumbar spine: 0. 490 g/cm~2,Z score:-0. 4). X-ray films indicated limb bone with local thickening,sclerosis,trabecular bone scratches,medullary stenosis,and bone at skull base and pelvic with local thickening and sclerosis. A heterozygous missense mutation c. 652 CT( p. R218 C) at exon 4 of TGFB1 was identified in the proband,but in neither of his parents. The patient was given glucocorticoid hormone therapy,and was followed up. Conclusion High bone turnover,cortical local thickening and sclerosis,trabecular bone scarcity,the medullary stenosis are typical clinical features of PDD,and TGFB1 gene c. 652 CT( p. R218 C) is one of pathogenic mutation of PDD. The clinical and biochemical finding in this patient with PDD would contributed to the diagnosis and treatment of PDD.
作者 李路娇 宋玉文 吕芳 徐晓杰 姜艳 王鸥 夏维波 邢小平 李梅 LI Lu-jiao, SONG Yu-wen, LYU Fang, XU Xiao-jie, JIANG Yan, WANG Ou, XIA Wei-bo, XING Xiao-ping, LI Mei (Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Beijing 100730, China)
出处 《中华骨质疏松和骨矿盐疾病杂志》 CSCD 北大核心 2018年第1期78-84,共7页
基金 国家自然科学基金面上项目(81570802) 国家重点研发计划(2016YFC0901501) 中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-003)
关键词 进行性骨干发育不良症 TGFB1基因突变 progressive diaphyseal dysplasia TGFB1 gene mutation
作者简介 通信作者:李梅,E-mail:limeilzh@sina.com
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  • 1朱瑞森,邱忠领,陆汉魁,陈立波,罗全勇.进行性骨干发育不良症99Tcm-MDP骨显像一例[J].中华核医学与分子影像杂志,2013(6). 被引量:2
  • 2顾东华,孙明,沈伟明.家族性进行性骨干发育异常三例[J].放射学实践,2011(1):109-110. 被引量:1
  • 3Bhadada SK, Sridhar S, Steenackers E, et al. Camurati-En- gelmann disease (progressive diaphyseal dysplasia) : reports of an Indian kindred [ J]. Calcif Tissue Int, 2014, 94: 240- 247. 被引量:1
  • 4Janssens K, Vanhoenacker F, Bonduelle M, et al. Camurati- Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment [J}. J Med Genet, 2006, 43: 1-11. 被引量:1
  • 5Whyte MP, Totty WG, Novack DV, et al. Camurati-En- gelmann disease: unique variant featuring a novel mutation in TGF-betal encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand [J]. J Bone Miner Res, 2011, 26: 920-933. 被引量:1
  • 6Wu S, Liang S, Yah Y, et al. A novel mutation of TGF- betal in a Chinese family with Camurati-Engelmann disease [J]. Bone, 2007, 40: 1630-1634. 被引量:1
  • 7Carlson ML, Beatty CW, Neff BA, et al. Skull base manifes- tations of Camurati-Engehnann disease [ J l. Arch Otolaryngol Head Neck Surg, 2010, 136: 566-575. 被引量:1
  • 8Khadilkar AV, Sanwalka NJ, Chiplonkar SA, et al. Norma- tive data and percentile curves for Dual Energy X-ray Absorp- tiometry in healthy Indian girls and boys aged 5 - 17 years [J]. Bone, 2011, 48: 810-819. 被引量:1
  • 9Kinoshita A, Saito T, Tomita H, et al. Domain-specific mu- tations in TGFB1 result in Camurati-Engelmann disease [ J]. Nat Genet, 2000, 26: 19-20. 被引量:1
  • 10Wang C, Zhang BH, Liu YJ, et al. Transforming growth fac- tor-betal gene mutations and phenotypes in pediatric patients with Camurati-Engelmann disease [ J]. Mol Med Rep, 2013, 7 : 1695-1699. 被引量:1

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