MNX1基因突变在Currarino综合征中的研究现状与进展  

Research advances of MNX1 mutations in Currarino syndrome

作　　者：刘凌娅 李龙[2] 姜茜[1] Liu Lingya;Li Long;Jiang Qian(Department of Medical Genetics,Capital Institute of Pediatrics,Beijing 100020,China;Department of General Surgery,Affiliated Children's Hospital Capital Institute of Pediatrics,Innovation Unit of Mini-Invasive Diagnosis&Treatment in Pediatric Surgery(2021RU015),Beijing 100020,China)

机构地区：[1]首都儿科研究所遗传研究室,北京100020 [2]首都儿科研究所附属儿童医院普通外科,中国医学科学院小儿外科微创诊疗创新单元(2021RU015),北京100020

出　　处：《中华小儿外科杂志》2023年第12期1145-1152,共8页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金(82070532);北京市属医学科研院所公益发展改革试点项目(京医研2019-11);中国医学科学院小儿外科微创诊疗创新单元(2021RU015)。

摘　　要：Currarino综合征是一种罕见的先天畸形,以骶骨、肛门直肠畸形与骶前肿物为典型表现,可伴多系统异常。根据患儿和成年患者的临床表型差异可分为完全型、轻型和微型。MNX1基因与Currarino综合征的发生密切相关。本文通过文献回顾,收集并分析145种MNX1致病变异携带者(297例)的临床表型及基因型信息,分析其临床特点及基因型-表型关联性。结果表明,Currarino综合征分型与突变位点的位置之间无明显关联,但累及MNX1基因的染色体变异携带者往往表型更重。突变位点的分布在MNX1基因的同源异形盒编码区内较为集中,这可能影响MNX1编码蛋白与特定下游靶基因的结合。罕见的MNX1纯合突变提示应关注Currarino综合征患儿的胰岛细胞功能。同一家系内携带相同MNX1突变的不同个体间表型差异大,提示存在其他调节因子。未来应在与MNX1存在显著相互作用蛋白的编码基因中继续寻找其他候选基因,重点关注参与胰腺、感觉器官发生、生殖结构发育等生物学过程的相关基因。Currarino syndrome(CS)is a rare congenital malformation characterized by three major clinical features of sacral agenesis,anorectal malformations and presacral mass.It can be divided into complete,mild and minimal CS according to clinical features.Besides the above triad,some patients may suffer from some abnormalities of multi-systems.MNX1 gene is closely correlated with the disease.The authors searched and collected the clinical and genotypic profiles of 297 mutation carriers.A total of 145 different MNX1 pathogenic variants related to CS have been reported in the literature so far.And patient phenotypes and clinical characteristics were recorded.No significant correlation existed between CS type and the location of mutation sites.However,chromosomal variation such as microdeletion of MNX1 gene coded for more serious phenotype.The distribution of mutation sites was concentrated in coding region of the homeodomain in MNX1.Mutations within homeodomain may alter DNA binding specificity.Furthermore,a rare homozygous mutation carrier of MNX1 hinted at a priority for islet function in CS patients.Different phenotypes of individuals carrying the same mutation within the same family may implicate the involvements of other regulators in the pathogenic mechanism.A new clue was detected for candidate genes in CS pathogenesis through enrichment analysis of 491 proteins interacting with MNX1 in early human embryonic developmental process.More attention should be devoted to the developments of pancreas,sensory organs and reproductive structures.

关 键 词：基因型 库拉里诺综合征 基因突变 

分 类 号：R725.9[医药卫生—儿科]