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NEJM：新的研究确定Pyle氏病的遗传性病因

2016-06-30 MedSci MedSci原创

骨脆性Pyle氏病遗传
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皮质骨脆性是骨质疏松症的一个共同的特点，与非脊椎骨折相关。目前难以做到调节皮质骨的动态平衡。探究骨骼的遗传性疾病或可为罕见疾病和常见的骨骼疾病的治疗开辟新的实验治疗方法。该研究评估了四例Pyle氏病患者，Pyle氏病是一种遗传性疾病，其特点是骨皮质变薄、肢体畸形、易骨折；两名患者由外显子测序法检测确定，其余两名患者通过Sanger测序确定。确定候选基因后，建立基因敲除小鼠模型，探究骨结构改变的机制

皮质骨脆性是骨质疏松症的一个共同的特点，与非脊椎骨折相关。目前难以做到调节皮质骨的动态平衡。探究骨骼的遗传性疾病或可为罕见疾病和常见的骨骼疾病的治疗开辟新的实验治疗方法。

该研究评估了四例Pyle氏病患者，Pyle氏病是一种遗传性疾病，其特点是骨皮质变薄、肢体畸形、易骨折；两名患者由外显子测序法检测确定，其余两名患者通过Sanger测序确定。确定候选基因后，建立基因敲除小鼠模型，探究骨结构改变的机制。

结果发现，四名患者的双等位基因截短突变发生于SFRP4，该基因编码分泌型卷曲相关蛋白4，一种可溶性的Wnt抑制剂。由于骨间隔间Wnt和骨形态发生蛋白（BMP）信号的调节差异，缺乏SFRP4小鼠（与人Pyle氏病相似）其骨小梁的数量增加，皮质骨异常薄。使用可溶性Bmp2受体（RAP-661）或使用硬化蛋白抗体治疗SFRP4缺乏的小鼠可纠正骨皮质缺损。

总而言之，该研究表明，Pyle氏病是由于缺乏 sFRP4而引起的，皮质骨和松质骨的动态平衡是由不同的机制控制的，sFRP4介导的Wnt和BMP信号的交叉调节是保持适当的骨皮质厚度和稳定性的关键。

原始出处：

Pelin O. Simsek Kiper,Hiroaki Saito, et al., Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease.N Engl J Med 2016; 374:2553-2562June 30, 2016DOI: 10.1056/NEJMoa1509342.


评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1859968, encodeId=62471859968a8, content=<a href='/topic/show?id=cc73951054b' target=_blank style='color:#2F92EE;'>#遗传性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95105, encryptionId=cc73951054b, topicName=遗传性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Tue Jan 31 03:04:00 CST 2017, time=2017-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129406, encodeId=d8341294068b, content=不错哦，会学到很多，喜欢梅斯医学文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sat Sep 17 11:44:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107376, encodeId=e68410e376c2, content=好文，值得学习，赞！, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Aug 30 11:15:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=91709, encodeId=eb1891e09d0, content=测序对于这种单基因遗传病那是非常容易，未来还可以通过基因编辑直接进行治疗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Fri Jul 01 13:23:00 CST 2016, time=2016-07-01, status=1, ipAttribution=)]
    2017-01-31 般若傻瓜

    #遗传性#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1859968, encodeId=62471859968a8, content=<a href='/topic/show?id=cc73951054b' target=_blank style='color:#2F92EE;'>#遗传性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95105, encryptionId=cc73951054b, topicName=遗传性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Tue Jan 31 03:04:00 CST 2017, time=2017-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129406, encodeId=d8341294068b, content=不错哦，会学到很多，喜欢梅斯医学文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sat Sep 17 11:44:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107376, encodeId=e68410e376c2, content=好文，值得学习，赞！, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Aug 30 11:15:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=91709, encodeId=eb1891e09d0, content=测序对于这种单基因遗传病那是非常容易，未来还可以通过基因编辑直接进行治疗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Fri Jul 01 13:23:00 CST 2016, time=2016-07-01, status=1, ipAttribution=)]
    2016-09-17 1e10c84am36(暂无匿称)

    不错哦，会学到很多，喜欢梅斯医学文章

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1859968, encodeId=62471859968a8, content=<a href='/topic/show?id=cc73951054b' target=_blank style='color:#2F92EE;'>#遗传性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95105, encryptionId=cc73951054b, topicName=遗传性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Tue Jan 31 03:04:00 CST 2017, time=2017-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129406, encodeId=d8341294068b, content=不错哦，会学到很多，喜欢梅斯医学文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sat Sep 17 11:44:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107376, encodeId=e68410e376c2, content=好文，值得学习，赞！, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Aug 30 11:15:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=91709, encodeId=eb1891e09d0, content=测序对于这种单基因遗传病那是非常容易，未来还可以通过基因编辑直接进行治疗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Fri Jul 01 13:23:00 CST 2016, time=2016-07-01, status=1, ipAttribution=)]
    2016-08-30 ylzr123

    好文，值得学习，赞！

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1859968, encodeId=62471859968a8, content=<a href='/topic/show?id=cc73951054b' target=_blank style='color:#2F92EE;'>#遗传性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95105, encryptionId=cc73951054b, topicName=遗传性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Tue Jan 31 03:04:00 CST 2017, time=2017-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129406, encodeId=d8341294068b, content=不错哦，会学到很多，喜欢梅斯医学文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sat Sep 17 11:44:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=107376, encodeId=e68410e376c2, content=好文，值得学习，赞！, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Aug 30 11:15:00 CST 2016, time=2016-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=91709, encodeId=eb1891e09d0, content=测序对于这种单基因遗传病那是非常容易，未来还可以通过基因编辑直接进行治疗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Fri Jul 01 13:23:00 CST 2016, time=2016-07-01, status=1, ipAttribution=)]
    2016-07-01 lovetcm

    测序对于这种单基因遗传病那是非常容易，未来还可以通过基因编辑直接进行治疗。

    0