Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.
Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.
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DOI：
10.3390/jcm10030481
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发表时间：
2021-01-28
影响因子：
3.9
通讯作者：
Janecke AR
中科院分区：
文献类型：
--
作者：
Aldrian D;Vogel GF;Frey TK;Ayyıldız Civan H;Aksu AÜ;Avitzur Y;Ramos Boluda E;Çakır M;Demir AM;Deppisch C;Duba HC;Düker G;Gerner P;Hertecant J;Hornová J;Kathemann S;Koeglmeier J;Koutroumpa A;Lanzersdorfer R;Lev-Tzion R;Lima R;Mansour S;Meissl M;Melek J;Miqdady M;Montoya JH;Posovszky C;Rachman Y;Siahanidou T;Tabbers M;Uhlig HH;Ünal S;Wirth S;Ruemmele FM;Hess MW;Huber LA;Müller T;Sturm E;Janecke AR
Myosin Vb （MYO5B）是一种马达蛋白，通过RAB11-和rab8依赖机制促进极化细胞中的蛋白质运输和再循环。在大多数微绒毛包涵性疾病（MVID）患者中发现双等位基因MYO5B突变。MVID是一种婴儿期难治性腹泻，具有特征性的组织病理学表现，需要终生肠外营养或肠移植。大量这样的患者最终发展为胆汁淤积性肝病。双等位基因MYO5B突变也在主要早发性胆汁淤积性肝病患者亚群中被发现。在这里，我们收集了114例MYO5B致病基因型患者，包括44例新患者和35例新MYO5B突变，并分析了MYO5B突变对功能的影响。我们的数据支持以下观点：(1)MYO5B蛋白的完全缺乏或MYO5B早期截断导致显性肠道疾病（MYO5B- mvid），(2)具有残留功能的全长突变MYO5B蛋白的表达导致显性胆汁淤积性肝病（MYO5B- pfic），以及(3)无残留功能的突变MYO5B蛋白的表达导致肠道和肝脏疾病（MYO5B- mixed）。基因型-表型数据存储在现有开放的MYO5B数据库中，以改善疾病诊断、预后和遗传咨询。
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.
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影响因子：
3.1
作者：
Schlegel C;Weis VG;Knowles BC;Lapierre LA;Martin MG;Dickman P;Goldenring JR;Shub MD
通讯作者：
Shub MD
影响因子：
3.9
作者：
Ruemmele, Frank M.;Mueller, Thomas;Huber, Lukas A.
通讯作者：
Huber, Lukas A.
影响因子：
5.3
作者：
Klee, Katharina M. C.;Janecke, Andreas R.;Vogel, Georg F.
通讯作者：
Vogel, Georg F.
影响因子：
158.5
作者：
CUTZ, E;RHOADS, JM;FORSTNER, GG
通讯作者：
FORSTNER, GG
TJP2的突变引起进行性胆汁淤积性肝病。
影响因子：
30.8
作者：
Sambrotta M;Strautnieks S;Papouli E;Rushton P;Clark BE;Parry DA;Logan CV;Newbury LJ;Kamath BM;Ling S;Grammatikopoulos T;Wagner BE;Magee JC;Sokol RJ;Mieli-Vergani G;University of Washington Center for Mendelian Genomics;Smith JD;Johnson CA;McClean P;Simpson MA;Knisely AS;Bull LN;Thompson RJ
通讯作者：
Thompson RJ