Gradual Loss of ACTH Due to a Novel Mutation in LHX4 Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism 英文参考文献.docVIP

下载本文档

12
0
约3.04万字
约 8页
2017-05-11 发布于上海
举报
版权申诉

Gradual Loss of ACTH Due to a Novel Mutation in LHX4 Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism 英文参考文献.doc

1、本文档共8页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Gradual Loss of ACTH Due to a Novel Mutation in LHX4 Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism 英文参考文献

GradualLossofACTHDuetoaNovelMutationinLHX4: ComprehensiveMutationScreeninginJapanesePatients withCongenitalHypopituitarism MasakiTakagi1,2,TomohiroIshii1,MikakoInokuchi1,NaokoAmano1,SatoshiNarumi1,YumiAsakura3, KojiMuroya3,YukihiroHasegawa2,MasanoriAdachi3,TomonobuHasegawa1* 1Department ofPediatrics,KeioUniversitySchoolofMedicineTokyo,Japan,2DepartmentofEndocrinologyandMetabolism,TokyoMetropolitanChildren’sMedical Center,Tokyo,Japan,3DepartmentofEndocrinologyandMetabolism,KanagawaChildren’sMedicalCenter,Kanagawa,Japan Abstract Mutationsintranscriptionfactorsgenes,whicharewellregulatedspatiallyandtemporallyinthepituitarygland,resultin congenitalhypopituitarism(CH)inhumans.TheprevalenceofCHattributabletotranscriptionfactormutationsappearsto berareandvariesamongpopulations. ThisstudyaimedtodefinetheprevalenceofCHintermsofnineCH-associated genesamongJapanesepatients.Weenrolled91JapaneseCHpatientsforDNAsequencingofPOU1F1,PROP1,HESX1,LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examinedbymultiplexligation-dependentprobeamplification.ThegeneregulatorypropertiesofmutantLHX4proteins were characterized in vitro. We identified twonovel heterozygous LHX4 mutations, namely c.249-1G.A, p.V75I, andone commonPOU1F1mutation,p.R271W.Thepatientharboringthec.249-1G.Amutationexhibitedisolatedgrowthhormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitaryhormonedeficiency.InvitroexperimentsshowedthatbothLHX4mutationswereassociatedwithanimpairmentof thetransactivationcapacitiesofPOU1F1andaGSU,withoutanydominant-negativeeffects.Thetotalmutationprevalencein Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic–pituitary -adrenal function is recommended for CH patients with LHX4 mutations. Citation: Takagi M, Ishii T, Inokuchi