AJHG：研究者发现引发Joubert综合征的关键致病基因

历史上，人类的科学和发现共同努力帮助受并发症影响的家庭成员制定相应的计划生育选择。C5ORF42是一个在魁北克St.Lawrence区域被识别出的引起Joubert综合征的关键致病基因，Joubert综合征是1969年发现的一种疾病综合征。近日来自蒙特利尔大学圣-朱斯蒂娜大学医院研究中心的研究人员对这种疾病进行了深入研究，相关研究成果刊登在了国际杂志The American Journal of Human Genetics上。

Joubert综合征可以影响患者的大脑发育、延缓精神运动发育、影响患者的眼球运动协调性以及引发呼吸异常。自从Marie Joubert博士和其同事于1969年描述了此病症后，和Joubert综合征相关的一些基因也在不同的人群中被发现，但是文章中，研究者所描述的魁北克形式的致病基因目前尚不清楚。

目前并没有相关研究来识别在魁北克疾病中的遗传起源，研究者解释道，这是首次研究在魁北克人群中出现的Joubert综合征，研究者将会给予家庭成员进行DNA测验以评估受Joubert综合征影响的儿童的遗传风险。这项研究既是遗传上的又是历史上的，自从Joubert综合征遍布全世界以后，遗传品系便出现了地域性的改变，Joubert综合征的分布和不同的人口历史有一定关系。

当然，魁北克地区并不是个例外，事实上，6000名法国加拿大移民大约在17世纪末到18世纪初定居在St.Lawrence区域定居，St.Lawrence的这些定居的居民的下降意味着一种创建者的遗传效应；的确，特定创建者的遗传突变也会转移至后代中去，这将增加后代的遗传疾病的风险。

实际上，研究小组识别出了三种C5ORF42突变，这些对于研究中的家庭都很常见，截止目前为止，研究发现了15个基因，在Joubert综合征的表达中扮演着重要的角色，Michaud博士的研究小组将会继续研究，以便更好地理解基因的具体功能以及每种突变的特定效应。（生物谷：T.Shen编译）

doi:10.1016/j.ajhg.2012.02.011
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Mutations in C5ORF42 Cause Joubert Syndrome in the French Canadian Population

Myriam Srour1, 11, Jeremy Schwartzentruber2, 11, Fadi F. Hamdan1, Luis H. Ospina3, Lysanne Patry1, Damian Labuda4, Christine Massicotte4, Sylvia Dobrzeniecka1, José-Mario Capo-Chichi1, Simon Papillon-Cavanagh4, Mark E. Samuels4, Kym M. Boycott5, Michael I. Shevell6, Rachel Laframboise7, Valérie Désilets4, FORGE Canada Consortium12, Bruno Maranda8, Guy A. Rouleau9, Jacek Majewski10 and Jacques L. Michaud1, ,

Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have not yet been identified in this family nor in most French Canadian individuals subsequently described. We ascertained a cluster of 16 JBTS-affected individuals from 11 families living in the Lower St. Lawrence region. SNP genotyping excluded the presence of a common homozygous mutation that would explain the clustering of these individuals. Exome sequencing performed on 15 subjects showed that nine affected individuals from seven families (including the original JBTS family) carried rare compound-heterozygous mutations in C5ORF42. Two missense variants (c.4006C>T [p.Arg1336Trp] and c.4690G>A [p.Ala1564Thr]) and a splicing mutation (c.7400+1G>A), which causes exon skipping, were found in multiple subjects that were not known to be related, whereas three other truncating mutations (c.6407del [p.Pro2136Hisfs31], c.4804C>T [p.Arg1602], and c.7477C>T [p.Arg2493]) were identified in single individuals. None of the unaffected first-degree relatives were compound heterozygous for these mutations. Moreover, none of the six putative mutations were detected among 477 French Canadian controls. Our data suggest that mutations in C5ORF42 explain a large portion of French Canadian individuals with JBTS.