來(lái)自Genentech公司、斯坦福大學(xué)醫(yī)學(xué)院,、加州大學(xué)舊金山分校等多處的研究人員利用一種高精度蛋白質(zhì)組學(xué),，識(shí)別出了與Jourbert綜合癥（Joubert syndrome, JS）等疾病相關(guān)的基因。這一研究成果公布在《細(xì)胞》（Cell）雜志上,。
Joubert綜合癥是一種遺傳疾病,，影響小腦和腦干的發(fā)育,，這些大腦區(qū)域協(xié)調(diào)動(dòng)作、調(diào)節(jié)呼吸,、吞咽,、心率和意識(shí)等基礎(chǔ)功能。這一最新研究證實(shí)了導(dǎo)致JS和cillia細(xì)胞結(jié)構(gòu)遺傳變化的關(guān)鍵信息,。
盡管這種疾病很罕見(jiàn),，但之前的研究已經(jīng)確定出了另外四個(gè)遺傳標(biāo)志物。研究人員相信這些發(fā)現(xiàn)具有重要意義,。Joubert綜合癥能導(dǎo)致發(fā)育遲緩,、運(yùn)動(dòng)協(xié)調(diào)性差、無(wú)規(guī)則呼吸,、視覺(jué)缺陷,、腎臟衰竭等。癥狀多使得診斷很困難,。研究人員發(fā)現(xiàn)RPGRIP1L基因的突變?yōu)檫M(jìn)行準(zhǔn)確的DNA檢測(cè)奠定了基礎(chǔ),。這篇論文描述了一種能抑制兩種特殊的cilia蛋白質(zhì)之間的相互作用的基因突變。
這項(xiàng)研究的發(fā)現(xiàn)增加了人們對(duì)JS這種病的進(jìn)一步認(rèn)識(shí)和了解,。這種基因的發(fā)現(xiàn)讓研究人員進(jìn)一步了解大腦,、視網(wǎng)膜和腎臟的發(fā)育，更好地了解正常和異常的大腦并最終找到治療相關(guān)疾病的有效方法,。
Jourbert綜合癥患者因小腦蚓部（cerebellar vermis）和腦干部分發(fā)育不良或畸形,，而有程度不一的病癥出現(xiàn)：包括缺乏肌肉控制力、呼吸過(guò)強(qiáng)（hypernea）,、眼睛和舌頭運(yùn)動(dòng)異常,、和腎臟方面等問(wèn)題。病癥的嚴(yán)重程度不一可能因基因修飾者的存在而影響疾病嚴(yán)重和表現(xiàn)程度,。此疾病相當(dāng)罕見(jiàn),，病患數(shù)量少不易進(jìn)行基因分析，因此相關(guān)基因研究相當(dāng)緩慢,。（生物谷Bioon.com）
生物谷推薦原文出處：
Cell DOI:10.1016/j.cell.2011.04.019
Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and Pathways
Liyun Sang, Julie J. Miller, Kevin C. Corbit, Rachel H. Giles, Matthew J. Brauer, Edgar A. Otto, Lisa M. Baye, Xiaohui Wen, Suzie J. Scales, Mandy Kwong, Erik G. Huntzicker, Mindan K. Sfakianos, Wendy Sandoval, J. Fernando Bazan, Priya Kulkarni, Francesc R. Garcia-Gonzalo, Allen D. Seol, John F. O'Toole, Susanne Held, Heiko M. Reutter, William S. Lane, Muhammad Arshad Rafiq, Abdul Noor, Muhammad Ansar, Akella Radha Rama Devi, Val C. Sheffield, Diane C. Slusarski, John B. Vincent, Daniel A. Doher
Nephronophthisis (NPHP), Joubert (JBTS), and Meckel-Gruber (MKS) syndromes are autosomal-recessive ciliopathies presenting with cystic kidneys, retinal degeneration, and cerebellar/neural tube malformation. Whether defects in kidney, retinal, or neural disease primarily involve ciliary, Hedgehog, or cell polarity pathways remains unclear. Using high-confidence proteomics, we identified 850 interactors copurifying with nine NPHP/JBTS/MKS proteins and discovered three connected modules: NPHP1-4-8 functioning at the apical surface, NPHP5-6 at centrosomes, and MKS linked to Hedgehog signaling. Assays for ciliogenesis and epithelial morphogenesis in 3D renal cultures link renal cystic disease to apical organization defects, whereas ciliary and Hedgehog pathway defects lead to retinal or neural deficits. Using 38 interactors as candidates, linkage and sequencing analysis of 250 patients identified ATXN10 and TCTN2 as new NPHP-JBTS genes, and our Tctn2 mouse knockout shows neural tube and Hedgehog signaling defects. Our study further illustrates the power of linking proteomic networks and human genetics to uncover critical disease pathways.
