皮肤骨膜增厚症家系遗传学研究  

Genetic analysis of a pedigree with primary hypertrophic osteoarthropathy

作　　者：刘晓钢[1] 李静怡[1] 白莹[1] 张丽侠[1] 吴雪[1] 马圆圆[1] 柴利杰 郑丽丽[1] 

机构地区：[1]郑州大学第一附属医院内分泌科,450000

出　　处：《中华内科杂志》2017年第3期194-198,共5页Chinese Journal of Internal Medicine

基　　金：河南省卫生和计划生育委员会基金资助项目（201203010）

摘　　要：目的通过对一皮肤骨膜增厚症家系遗传学研究，结合国内外相关文献资料，进一步阐述其临床特点及遗传学发病机制。方法总结、分析一中国汉族皮肤骨膜增厚症家系的临床资料，抽取先证者及部分亲属的外周血，提取基因组DNA，PCR扩增后，采用Sanger法对HPGD基因全外显子测序，将测序结果与美国国立生物技术信息中心（NCBI）的参考序列进行比较寻找突变位点并进行遗传学分析。结果（1）先证者为儿童时期发病，主要临床表现为杵状指、多汗、皮脂溢、关节肿胀等，X线可发现管状骨骨膜增厚及骨质增生；（2）先证者为HPGD基因3号外显子上c.310_311delCT纯合突变，其父母均为该位点杂合突变携带者，其姐姐未发现突变；（3）蛋白空间结构预测显示突变蛋白与野生型蛋白相比，肽链改变约60%，缺失大量与辅酶、前列腺素E2（PGE2）结合区域以及酶活性位点。结论皮肤骨膜增厚症的临床表现及X线检查有助于诊断，基因检测可以确诊该病。HPGD基因突变引起15-羟基前列腺素脱氢酶结构及功能发生改变，导致皮肤骨膜增厚症发生。Objective To analyze the clinical and genetic features of primary hypertrophic osteoarthropathy （PHO）. Methods The clinical data of one Chinese pedigree of PHO, namely pachydermoperiostosis （PDP） were collected. Blood samples were drawn from the propositus and other family members. DNA was extracted and genetic analysis was performed by Sanger method after PCR. The sequencing data of HPGD gene exons were analyzed by alignment with sequences from National Center for Biotechnology Information （NCBI）. Results （1）The propositus represented symptoms in childhood including clubbing fingers, sweating, seborrhea, joint swelling and so on. Periosteal thickening and bone hyperplasia were found by X-ray. （2） The homozygous mutation named c. 310_311delCT in propositus, which located in the third exon of HPGD, was identified. His parents carried the same heterozygous mutation, while his sister did not inherit any mutation of this gene. （3） The prediction of spatial structure of proteins revealed that the mutant proteins had about 60% discrepancy compared with wild-type protein, losing a lot of motifs responsible for combining with coenzyms and prostaglandin E2, as well as active sites of enzymes. Conclusions The clinical manifestations and imaging findings are helpful to diagnose PDP. Moreover gene mutation analysis ensures the diagnosis. The structure and function of HPGD gene mutation induce 15-hydroxy prostaglandin dehydrogenase mutation, contributing to the occurrence of PDP.

关 键 词：皮肤骨膜增厚症 HPGD基因 杵状指(趾) 

分 类 号：R684[医药卫生—骨科学]