TRPV4基因突变导致Kozlowski型脊柱干骺端发育不良病一例家系研究  

Investigation of one pedigree diagnosed as Kozlowski type spondylometaphyseal dysplasia caused by TRPV4 mutation

作　　者：程健豪 傅文贞[1] 何进卫[1] 汪纯[1] 章振林[1] CHENG Jian-hao, FU Wen-zhen, HE Jin-wei, WANG Chun, ZHANG Zhen-lin(Metabolic Bone diseases and Genetic Research Unit, Department of Osteoporosis and Bone Diseases Shanghai Jiaotong University affiliated Sixth People＇s Hospital, Shanghai 200233, Chin)

机构地区：[1]上海交通大学附属第六人民医院骨质疏松与骨病专科,上海200233

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2018年第2期160-165,共6页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(81270964);科技部973重大研究项目(2014CB942903)

摘　　要：目的 Kozlowski型脊柱干骺端发育不良(Kozlowski type spondylometaphyseal dysplasia,SMDK)是一种罕见的常染色显性遗传病。本文报道了1例SMDK患者家系的临床特征,并进行致病基因突变检测,同时复习相关文献。方法 1例SMDK先证者及其患病母亲及5例健康家庭成员,外周血抽提基因组DNA进行瞬时感受器电位离子通道亚家族蛋白4编码基因(transient receptor potentialcation channel subfamily V member4,TRPV4)16个外显子Sanger测序,并以100名健康志愿者作为基因突变分析的对照。同时对先证者和其母亲进行体格,生化及放射学检查。结果先证者及其母亲临床表现为髋内翻畸形,膝外翻畸形,脊柱侧弯且伴有干骺端的改变。Sanger测序显示TRPV4基因(c.1781G>A)杂合突变,其他家族成员及健康对照者均未发现相同突变。结论本研究发现的TRPV4基因11号外显子错义突变(c.1781G>A)为该家系致病突变。Objective Kozlowski type spondylometaphyseal dysplasia （SMDK） is a rare autosomal dominant disease. The clinical manifestation of a pedigree diagnosed with SMDK was reported and mutation was screened for her family. Methods Genomic DNA was extracted from the patient and her mother, their 5 healthy relatives and 100 unrelated healthy volunteers as controls. Sanger sequencing was conducted to screen the gene mutation. Results The clinical manifestation of the proband and her mother included varus deformity, knee valgus deformity, scoliosis and metaphyseal change. Sanger sequencing revealed heterozygote mutation （c. 1781G〉A） in exon 11 of TRPV4 gene, which was not found in their other family members and healthy controls. Conclusion The missense mutation c. 1781G〉A of the TRPV4 was the genetic pathogeny of SMDK in this case.

关 键 词：Kozlowski型脊柱干骺端发育不良 TRPV4基因 突变 

分 类 号：R681[医药卫生—骨科学]