间向性骨发育不良一家系及其瞬时感受电位香草酸家族4基因突变  

Clinical and genetic study on a family with metatropic dysplasia due to transient receptor potential vanilloid 4 gene mutation

作　　者：朱青[1] 孟岩[1] 邹丽萍[1] 

机构地区：[1]中国人民解放军总医院儿童医学中心儿内科,北京100853

出　　处：《中华实用儿科临床杂志》2016年第8期609-612,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家科技支撑计划项目（2013BA112801-1）;北京市科技计划项目（Z141100002114001）

摘　　要：目的总结问向性骨发育不良1家系中患者的临床特征和遗传学资料，以提高对本病的认识和诊断水平。方法先证者为1岁男童，患儿母亲26岁，分析其临床表现、影像学资料、瞬时感受电位香草酸家族4（TRPV4）基因突变检测结果。结果患儿主要表现为大头、前额突出、鼻梁低平、面中部发育不良、胸廓窄长、胸骨隆起、肋骨外翻、脊柱后凸、四肢较躯干相对短小。x线片显示椎体扁平，脊柱后凸，肋骨增宽，后端杯口状变形，四肢长管状骨干骺端扩张，骨骺出现延迟，发育小，形态不规则。其母身高、面容正常，脊柱侧突。X线片显示胸椎向右侧侧弯畸形，椎体密度减低，形态异常，椎间隙变窄，股骨及胫骨干骺端未见异常。先证者和母亲TRPV4基因检测发现均存在1个c．2396〉T（P．P799L）的杂合突变，为已知突变。结论先证者和母亲均为TRPV4基因突变导致的先天骨骼畸形，先证者具有间向性骨发育不良的典型改变，母亲症状轻。TRPV4基因相关的脊柱骨骺发育异常患者的临床表型、影像学改变存在较高的异质性，基因突变检测是确诊的关键。Objective To summarize the clinical,radiographic and genetic features of a family with metatropic dysplasia,in order to improve the level of understanding and diagnosis of this disease. Methods The proband, a one - year old boy, was diagnosed as metatropic dysplasia. His mother was 26 years old with mildly phenotype. Their clinical features and bone X - ray findings were analyzed. The DNA samples of the proband and his parents were collected. The coding exons and flanking introns regions of transient receptor potential vanilloid 4 （TRPV4） gene were amplified by polymerase chain reaction （PCR） and analyzed by DNA automatic detector. The pathology, diagnosis, treatment and prognosis were expounded. Results The symptoms of the boy were characterized by short extremities, a short trunk with progressive kyphoscoliosis, and craniofacial abnormalities that include a prominent forehead, midface hypoplasia, and a squared - off jaw. His motor development was slightly delayed. Mental development was normal. Bone X ray of the boy showed platyspondyly and severe metaphyseal enlargement with shortening of long bones and irregularities and de- layed ossification of epiphysis. The patient and his mother were heterozygous for the nucleotide substitutions c. 2396 〉 T （p. P799L） in TRPV4 gene. Conclusions The patient and his mother with metatropic dysplasia were diagnosed with TRPV4 gene analysis. The patient showed typical clinical features. His mother was mild. Metatropic dysplasia had signi- ficantly clinical heterogeneity. Gene analysis is helpful for the diagnosis.

关 键 词：脊柱骨骺发育不良 间向性骨发育不良 瞬时感受电位香草酸家族4通道蛋白 瞬时感受电位 香草酸家族4基因突变 

分 类 号：R726.8[医药卫生—儿科]