一國(guó)際研究小組最近發(fā)現(xiàn)，一種以前未知的TMEM216基因變異可導(dǎo)致新生兒患上嚴(yán)重的美—格二氏綜合征（Meckel-Gruber）和Joubert綜合征,，這兩種導(dǎo)致嬰兒嚴(yán)重畸形的疾病困擾著許多的家庭,。而該致病基因的發(fā)現(xiàn)不僅會(huì)有助于降低畸形嬰兒的出生比例，也使科學(xué)家對(duì)胎兒發(fā)育過(guò)程有了更清晰的認(rèn)識(shí),。
發(fā)表在最新一期《自然·遺傳學(xué)》雜志上的研究報(bào)告稱,，由英國(guó)利茲大學(xué)及巴黎、羅馬等地的遺傳學(xué)家組成的國(guó)際研究小組,，通過(guò)對(duì)畸形兒童及有此疾病家族史的人的DNA進(jìn)行分析,，確認(rèn)一種以前從未認(rèn)知的TMEM216基因變異可導(dǎo)致嬰兒患上美—格二氏綜合征和Joubert綜合征。研究人員發(fā)現(xiàn),，該致病基因會(huì)導(dǎo)致細(xì)胞的纖毛無(wú)法對(duì)信息進(jìn)行甄別和回復(fù),，從而妨礙胎兒神經(jīng)索的正常發(fā)育，導(dǎo)致胎兒大腦發(fā)育異常,，而受此影響的胎兒會(huì)出現(xiàn)眼睛畸形,、多一個(gè)手指或腳趾、脊柱裂或多腎囊等發(fā)育異常狀況,。
美—格二氏綜合征和Joubert綜合征是十分典型的新生兒畸形發(fā)育疾病,，困擾著無(wú)數(shù)的家庭。這兩種疾病都是隱性遺傳疾病,，只有夫妻二人都具有致病基因,，才會(huì)使下一代發(fā)病。但胎兒發(fā)育的這些缺陷往往只有在懷孕12周之后進(jìn)行超聲波檢查才有可能被發(fā)現(xiàn),。因而確認(rèn)該種疾病的遺傳基因十分重要,，這使得通過(guò)基因篩選來(lái)預(yù)知胎兒畸形發(fā)育的風(fēng)險(xiǎn)成為可能。
研究人員表示,，精確的TMEM216基因檢測(cè),，對(duì)于那些有著畸形發(fā)育家族史的家庭來(lái)說(shuō)極其重要，可使他們避免孩子嚴(yán)重畸形的慘痛后果,。而同時(shí),，TMEM216基因的發(fā)現(xiàn)也有助于科學(xué)家對(duì)胎兒發(fā)育過(guò)程中信號(hào)通路的作用有了更明確的理解。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Genetics doi:10.1038/ng.594
Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes
Enza Maria Valente1,2,24, Clare V Logan3,24, Soumaya Mougou-Zerelli4,5,24, Jeong Ho Lee6,24, Jennifer L Silhavy6, Francesco Brancati1,7, Miriam Iannicelli1, Lorena Travaglini1, Sveva Romani1, Barbara Illi1, Matthew Adams3, Katarzyna Szymanska3, Annalisa Mazzotta1, Ji Eun Lee6, Jerlyn C Tolentino6, Dominika Swistun6, Carmelo D Salpietro2, Carmelo Fede2, Stacey Gabriel8, Carsten Russ8, Kristian Cibulskis8, Carrie Sougnez8, Friedhelm Hildebrandt9, Edgar A Otto9, Susanne Held9, Bill H Diplas10, Erica E Davis10, Mario Mikula11, Charles M Strom11, Bruria Ben-Zeev12, Dorit Lev13, Tally Lerman Sagie13, Marina Michelson13, Yuval Yaron14, Amanda Krause15, Eugen Boltshauser16, Nadia Elkhartoufi17, Joelle Roume18, Stavit Shalev19, Arnold Munnich4,17, Sophie Saunier20, Chris Inglehearn3, Ali Saad5, Adila Alkindy21,23, Sophie Thomas4, Michel Vekemans4,17, Bruno Dallapiccola22, Nicholas Katsanis10, Colin A Johnson3,25, Tania Attié-Bitach4,17,25 & Joseph G Gleeson6,25
Joubert syndrome (JBTS), related disorders (JSRDs) and Meckel syndrome (MKS) are ciliopathies. We now report that MKS2 and CORS2 (JBTS2) loci are allelic and caused by mutations in TMEM216, which encodes an uncharacterized tetraspan transmembrane protein. Individuals with CORS2 frequently had nephronophthisis and polydactyly, and two affected individuals conformed to the oro-facio-digital type VI phenotype, whereas skeletal dysplasia was common in fetuses affected by MKS. A single G218T mutation (R73L in the protein) was identified in all cases of Ashkenazi Jewish descent (n = 10). TMEM216 localized to the base of primary cilia, and loss of TMEM216 in mutant fibroblasts or after knockdown caused defective ciliogenesis and centrosomal docking, with concomitant hyperactivation of RhoA and Dishevelled. TMEM216 formed a complex with Meckelin, which is encoded by a gene also mutated in JSRDs and MKS. Disruption of tmem216 expression in zebrafish caused gastrulation defects similar to those in other ciliary morphants. These data implicate a new family of proteins in the ciliopathies and further support allelism between ciliopathy disorders.
