人体TFG-β1基因的缺失会导致小儿IBD及相关脑病
Title：
Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy
Abstract：
Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis. Following its discovery, enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties, pro- and anti-inflammatory effects, or pro- and anti-fibrinogenic characteristics. Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1-LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans.
All Authors：
Daniel Kotlarz,Benjamin Marquardt,Tuva Barøy,Way S Lee,Liza Konnikova,Sebastian Hollizeck,Thomas Magg,Anna S Lehle,Christoph Walz,Ingo Borggraefe,Fabian Hauck,Philip Bufler,Raffaele Conca,Sarah M Wall,Eva M Schumacher,Doriana Misceo,Eirik Frengen,Beint S Bentsen,Holm H Uhlig,Karl-Peter Hopfner,Aleixo M Muise,Scott B Snapper,Petter Strømme,Christoph Klein
First Authors：
Daniel Kotlarz
Correspondence：
Christoph Klein
摘要：
TGF-β1（由TGFB1基因编码）与胚胎形成、发育、组织稳态、炎症、促癌/抑癌平衡、促炎/抑炎平衡、促纤维蛋白原/抗纤维蛋白原平衡相关； 在2个家系中存在3个个体，携带TGFB1双等位基因的功能缺失突变的个体表现出严重的小儿IBD，以及与癫痫、脑萎缩、后脑白质病变相关的中枢神经系统疾病；突变的TGFB1等位基因编码的蛋白表现出受损的分泌功能，以及TGF-β1-LAP复合体的功能及稳定性受损，从而导致TGF-β1的生物利用度降低。