PLoS Genet:编码限制性羧基末端结构域的SLC12A2变异体能够引起人类遗传性听力损失

2020-05-11 AlexYang MedSci原创

由于致病基因的遗传异质性,遗传性听力损失的诊断比较有挑战性。到目前为止,仍旧有一些遗传性听力损失相关基因需要鉴定。

由于致病基因的遗传异质性,遗传性听力损失的诊断比较有挑战性。到目前为止,仍旧有一些遗传性听力损失相关基因需要鉴定。

最近,有研究人员使用全外显子组分析对3个具有先天性、重度到永久性听力损失家庭中进行了研究,并在1个家庭的5为成员中鉴定了SLC12A2的一个错义突变,且是显性模式;同时还有2例散发性病例,分别为SLC12A2剪接位点变异和错义变异,这些均是听力损失相关的候选位点。更多的是,研究人员还在1个散发性病例中检测到了SLC12A2的一个新错义变异。SLC12A2编码Na+、K+和2Cl-共转运子(NKCC)1,并且在K+富集的内淋巴的稳态中起关键作用。Slc12a2缺陷小鼠具有先天永久性听力损失。所有鉴定的SLC12A2变异均定位在第21个外显子或者其3'剪接位点。体外分析表明了在耳蜗中,剪接位点变异能够产生缺失第21个外显子的SLC12A2 mRNA转录本,并且其表达要比包含第21个外显子的转录本低的多,表明了第21个外显子对SLC12A2的表达具有组织特异性作用。体外功能分析阐释了Cl输入在所有的SLC12A2变异体中减少。免疫组化分析阐释了SLC12A2定位在耳蜗中一些类型细胞的细胞膜上,包括了对内淋巴稳态很重要的边缘细胞。

最后,研究人员指出,他们的研究表明了能够影响SLC12A2转录的第21个外显子变异与人类遗传性听力损失相关。

原始出处:

Mutai H, Wasano K, Momozawa Y et al. Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans. PLoS Genet. 15 April 2020.

 

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    2020-05-24 liubm568
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    2020-05-13 canlab
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encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Mon May 18 04:17:58 CST 2020, time=2020-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1926360, encodeId=91c01926360b8, content=<a href='/topic/show?id=0c72e85900c' target=_blank style='color:#2F92EE;'>#结构域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78590, encryptionId=0c72e85900c, topicName=结构域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=734374, createdName=gjsgj, createdTime=Tue Jun 09 10:17:58 CST 2020, time=2020-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686336, encodeId=6ca616863369d, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584767, encodeId=6c0e1584e67cc, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Wed May 13 04:17:58 CST 2020, time=2020-05-13, status=1, ipAttribution=)]
    2020-05-18 cy0324
  5. [GetPortalCommentsPageByObjectIdResponse(id=1860112, encodeId=e7ce18601121f, 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=26, 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=Sun Jul 26 16:17:58 CST 2020, time=2020-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1770516, encodeId=d72e1e70516fe, content=<a href='/topic/show?id=05fe2665508' target=_blank style='color:#2F92EE;'>#体能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26655, encryptionId=05fe2665508, topicName=体能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=80ae38174281, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584767, encodeId=6c0e1584e67cc, content=<a href='/topic/show?id=83f5e9250e9' target=_blank style='color:#2F92EE;'>#编码#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79250, encryptionId=83f5e9250e9, topicName=编码)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b10a17056098, createdName=12498f6em12暂无昵称, createdTime=Wed May 13 04:17:58 CST 2020, time=2020-05-13, status=1, ipAttribution=)]
    2020-06-09 gjsgj
  6. [GetPortalCommentsPageByObjectIdResponse(id=1860112, encodeId=e7ce18601121f, 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=26, 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=Sun Jul 26 16:17:58 CST 2020, time=2020-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1770516, encodeId=d72e1e70516fe, content=<a href='/topic/show?id=05fe2665508' target=_blank style='color:#2F92EE;'>#体能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26655, encryptionId=05fe2665508, topicName=体能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=80ae38174281, 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  7. 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    2020-05-13 ysjykql
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