一国际研究小组最近发现，一种以前未知的TMEM216基因变异可导致新生儿患上严重的美―格二氏综合征（Meckel-Gruber）和Joubert综合征，这两种导致婴儿严重畸形的疾病困扰着许多的家庭。而该致病基因的发现不仅会有助于降低畸形婴儿的出生比例，也使科学家对胎儿发育过程有了更清晰的认识。
发表在最新一期《自然遗传学》杂志上的研究报告称，由英国利兹大学及巴黎、罗马等地的遗传学家组成的国际研究小组，通过对畸形儿童及有此疾病家族史的人的DNA进行分析，确认一种以前从未认知的TMEM216基因变异可导致婴儿患上美―格二氏综合征和Joubert综合征。研究人员发现，该致病基因会导致细胞的纤毛无法对信息进行甄别和回复，从而妨碍胎儿神经索的正常发育，导致胎儿大脑发育异常，而受此影响的胎儿会出现眼睛畸形、多一个手指或脚趾、脊柱裂或多肾囊等发育异常状况。
美―格二氏综合征和Joubert综合征是十分典型的新生儿畸形发育疾病，困扰着无数的家庭。这两种疾病都是隐性遗传疾病，只有夫妻二人都具有致病基因，才会使下一代发病。但胎儿发育的这些缺陷往往只有在怀孕12周之后进行超声波检查才有可能被发现。因而确认该种疾病的遗传基因十分重要，这使得通过基因筛选来预知胎儿畸形发育的风险成为可能。
研究人员表示，精确的TMEM216基因检测，对于那些有着畸形发育家族史的家庭来说极其重要，可使他们避免孩子严重畸形的惨痛后果。而同时，TMEM216基因的发现也有助于科学家对胎儿发育过程中信号通路的作用有了更明确的理解。
生物谷推荐原文出处：
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.
