进行性骨干发育不良致病基因鉴定  

Identification of pathogenic genes of progressive diaphyseal dysplasia

作　　者：杨文迪 陶晓卉 徐甜 章振林 岳华 YANG Wen-di;TAO Xiao-hui;XU Tian;ZHANG Zhen-lin;YUE Hua(Department of Osteoporosis and Bone Diseases,Shanghai Sixth Peoples Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Clinical Research Center of Bone Disease,Shanghai 200233,China)

机构地区：[1]上海交通大学医学院附属第六人民医院骨质疏松和骨病专科,上海市骨疾病临床研究中心,上海200233

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2023年第5期450-457,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(81770874,81974126,82270932)。

摘　　要：目的 通过对临床拟诊的进行性骨干发育不良(progressive diaphyseal dysplasia, PDD)患者进行致病基因鉴定,明确疾病诊断并进一步分析疾病临床特征、生化特点及影像学改变。方法 本研究收集1例因“下肢疼痛伴步态异常17年”,在骨质疏松与骨病专科门诊就诊的20岁男性患者临床资料,根据其症状、体征,临床拟诊PDD。经完善辅助检查,并采用Sanger测序法检测患者及家系成员转化生长因子β1(transforming growth factor beta 1,TGFβ1)基因突变位点。结果 Sanger测序证实患者存在TGFβ1基因4号外显子c.652C>T(p.Arg218Cys)杂合错义突变,家系内其他成员未检测出上述突变。随后在250例健康对照中进一步验证,未检测出该基因存在突变。结论 TGFβ1为导致PDD的致病基因,4号外显子c.652C>T(p.Arg218Cys)突变为热点突变。PDD起病早,病变累及四肢长骨伴肌组织菲薄,导致步态异常、行走困难,严重影响生命质量。Objective To identify the causative gene and explore the clinical characteristics,biochemical indi-cators,and radiological features in a patient with progressive diaphyseal dysplasia(PDD).Methods A 20-year-old male patient complained of“lower limbs pain with abnormal gait for 17 years”was recruited in our study,clinical data and supplementary examinations were collected.Transforming growth factor beta 1(TGFβ1)gene mutation was identified in patients and family members by using Sanger sequencing.Results Heterozygous mutation of TGFβ1 c 652C>T(p Arg218Cys)was detected by Sanger sequencing.No mutation was found in other family members.Conclusion TGFβ1 is the pathogenic gene leading to PDD,and c 652C>T(p Arg218Cys)in exon 4 is a hot spot mutation.PDD is early onset and involves long bones in the limbs with thin muscle tissue,leading to abnormal gait and limited mobility,se-riously affecting quality of life.

关 键 词：进行性骨干发育不良 转化生长因子Β1 基因突变 

分 类 号：R681[医药卫生—骨科学]