J Lipid Res:从以色列到日本,国际合作揭开罕见病病因

2018-06-01 小通 生物通

年前,一名婴儿出生在以色列海法的Rambam医学中心。他刚出生时状况良好,但两小时后癫痫发作。医务人员立即将他转移到新生儿重症监护病房,并开展各项检查,以便尽快做出诊断。然而,每项结果都是阴性的。这名婴儿到底怎么啦?

年前,一名婴儿出生在以色列海法的Rambam医学中心。他刚出生时状况良好,但两小时后癫痫发作。医务人员立即将他转移到新生儿重症监护病房,并开展各项检查,以便尽快做出诊断。然而,每项结果都是阴性的。这名婴儿到底怎么啦?



答案过了很多年才揭晓。如今,Rambam医学中心、日本RIKEN脑科学研究所,以及其他机构的研究人员在《The Journal of Lipid Research》的6月刊上公布了他们解开这个医学谜团的方法。

一种神秘的遗传病

新生儿癫痫发作可能有多种原因,不过,这名婴儿的十多项常规检查都正常。他没有感染,也没有已知代谢物的问题,尿液和脑脊液也没有提供线索。Hanna Mandel博士是Rambam医院的代谢病专家,也是当时的团队负责人。他表示,他们无法解释孩子的疾病。

于是,医疗团队将这个三周大的孩子送去进行脑部扫描。图像显示他缺乏髓磷脂,即神经周围的必要脂肪层。髓磷脂就像电线周围的塑料绝缘体一样。如果没有绝缘体,那么电线(这里指神经元)就无法很好地传输电信号。专家认为,这种缺陷可能影响男孩的发育。

当这个男孩4岁大时,耶路撒冷希伯来大学医学中心的罕见病专家Orly Elpeleg带领团队测序并分析了他的基因组,以寻找他携带的遗传突变。

研究人员在13个基因组位点上发现了十分罕见的变异。最终,研究人员确定致病突变在一个叫做EPT1的基因上。与健康对照相比,患者编码EPT1蛋白的mRNA明显缩短。这是患者首次被诊断出带有EPT1突变。于是,Mandel博士开始求助世界各地的专家。

国际友人来帮忙

在日本著名的RIKEN脑科学研究所,团队负责人Yoshio Hirabayashi博士以及博士后研究员Yasuhiro Horibata曾经开展EPT1的研究。他们两人发现,EPT1编码的酶负责磷脂酰乙醇胺(PE)生产过程中的收尾工作,并于2007年发表了这项结果。

Mandel找到那篇论文,并写信给Hirabayashi。不久,他们三人就决定合作。以色列的团队将这个孩子的组织样本送往日本。日本的团队测定了细胞中的酶活性,并证实远远低于健康对照。

接着,他们开始寻找皮肤细胞的变化,测定细胞产生的所有脂质。让他们惊讶的是,EPT1的缺乏只是导致组织中的磷脂酰乙醇胺量略微减少。这是意想不到的, 因为PE 是 EPT1已知的主要产物。

然而,EPT1的缺乏导致另一种分子的数量大大减少,这就是髓磷脂中富含的缩醛磷脂。儿童的细胞似乎能够利用其他酶来补偿磷脂酰乙醇胺的生产,但是无法拯救缩醛磷脂合成的不足。研究人员总结道,即使磷脂酰乙醇胺的生产工作由其他酶替代,但EPT1仍然是大脑中合成髓磷脂所必需的。

至此,研究人员终于解开了这种神秘疾病背后的谜团。不过,这个男孩的治疗手段仍有限。如今,他失明失聪,癫痫发作频繁。不过,他在家乡附近的一个康复中心接受康复治疗。未来,他的父母在生育时会考虑胚胎植入前遗传学诊断。

原始出处:

Yasuhiro Horibata,et al.Ethanolamine phosphotransferase 1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in human.J Lipid Res. First Published on March 2, 2018, doi:10.1194/jlr.P081620

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    2018-08-20 bettycmoon
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    2018-06-03 syscxl
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    2018-06-02 三生有幸9135

    学习一下谢谢

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2080578, encodeId=90c720805e832, content=<a href='/topic/show?id=ea824109e1c' target=_blank style='color:#2F92EE;'>#国际合作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41097, encryptionId=ea824109e1c, topicName=国际合作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ed25376, createdName=gdsun, createdTime=Sun Nov 25 06:15:00 CST 2018, time=2018-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656387, encodeId=6d5f165638efb, content=<a href='/topic/show?id=6e6a1091e1e' target=_blank style='color:#2F92EE;'>#Lipid#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10917, encryptionId=6e6a1091e1e, topicName=Lipid)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=66a524807292, createdName=bettycmoon, createdTime=Mon Aug 20 15:15:00 CST 2018, time=2018-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1294412, encodeId=a94812944123b, content=<a href='/topic/show?id=ca6e592189b' target=_blank style='color:#2F92EE;'>#日本#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59218, encryptionId=ca6e592189b, topicName=日本)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sun Jun 03 14:15:00 CST 2018, time=2018-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1467322, encodeId=0f59146e3227b, content=<a href='/topic/show?id=ef32e9539e8' target=_blank style='color:#2F92EE;'>#罕见#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79539, encryptionId=ef32e9539e8, topicName=罕见)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=29f36868190, createdName=syscxl, createdTime=Sun Jun 03 14:15:00 CST 2018, time=2018-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320731, encodeId=0a0f320e3131, content=学习一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sat Jun 02 06:55:47 CST 2018, time=2018-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320677, encodeId=0b7d3206e726, content=年前.一名婴儿出生在以色列海法的Rambam医学中心.他刚出生时状况良好.但两小时后癫痫发作.医务人员立即将他转移到新生儿重症监护病房.并开展各项检查.以便尽快做出诊断.然而.每项结果都是阴性的.这名婴儿到底怎么啦?, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Sat Jun 02 05:33:01 CST 2018, time=2018-06-02, status=1, ipAttribution=)]
    2018-06-02 有备才能无患

    年前.一名婴儿出生在以色列海法的Rambam医学中心.他刚出生时状况良好.但两小时后癫痫发作.医务人员立即将他转移到新生儿重症监护病房.并开展各项检查.以便尽快做出诊断.然而.每项结果都是阴性的.这名婴儿到底怎么啦?

    0