MAB21L2基因变异致小眼畸形2例及MAB21L1和MAB21L2的基因型-表型的系统回顾研究  

Two cases of microphthalmia caused by MAB21L2 gene mutation and a systematic review of genotype-phenotype associations of MAB21L1 and MAB21L2

作　　者：董怡君 刘梦楚 易珍 张清炯[1] 王攀峰[1] DONG Yijun;LIU Mengchu;YI Zhen;ZHANG Qingjiong;WANG Panfeng(State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou 510060,China)

机构地区：[1]中山大学中山眼科中心,眼病防治全国重点实验室,广东省眼科视觉科学重点实验室,广州510060

出　　处：《眼科学报》2024年第2期75-83,共9页Eye Science

基　　金：广州市科技计划项目(202201011073)。

摘　　要：目的:总结MAB21L2基因的变异和临床特点,并与高度同源的MAB21L1基因进行比较。方法:对中山眼科中心临床基因数据库中MAB21L2基因变异患者进行基因型和表型分析,回顾性分析既往文献报道的MAB21L2基因和高度同源基因MAB21L1变异的表型-基因型的关系。结果:在2个小眼畸形家系中发现2个MAB21L2基因杂合变异:先证者1携带已知变异c.151C>G/p.(Arg51Gly),患者双眼小眼畸形伴虹膜脉络膜缺损,伴骨关节屈曲。母亲携带相同杂合变异但表型正常;先证者2携带未报道的变异c.1042G>T/p.(Glu348*),左眼小眼畸形,右眼正常且无全身异常。结合文献回顾发现,在显性遗传模式下,80%的MAB21L2杂合致病变异(20/25)和100%的MAB21L1杂合致病变异(25/25)发生在氨基酸49-52区域,导致小眼无眼或眼缺损异常(microphthalmia,anophthalmia or coloboma,MAC);携带该区域MAB21L2基因杂合突变的患者除MAC外,部分还伴骨骼关节发育异常(12/24,50%);杂合截短变异发生在MAB21L2基因可导致MAC(5/5,100%),而发生在MAB21L1则不致病。结论:在2个小眼畸形家系中发现了MAB21L2基因1个新致病变异和1个已知热点致病变异,通过文献综述比较和总结了MAB21L1和MAB21L2基因的突变频谱以及基因型-表型相互关系,为此类基因缺陷导致遗传病的诊断和鉴别诊断提供依据。Objective:To summarize the genetic variations and clinical features of the MAB21L2 and compare them with the highly homologous MAB21L1 gene.Methods:A genotype-genotype analysis was performed on the patients with MAB21L2 gene variants in the clinical genetic database of Zhongshan Ophthalmic Center,Sun Yat-sen University.A retrospective review was undertaken to analyze the phenotype-genotype correlations of MAB21L2 gene variants and the highly homologous MAB21L1 gene variants reported in the previous literature.Results:Two heterozygous MAB21L2 gene variants were identified in two families with microphthalmia:Proband 1 carried the known variant c.151C>G/p.(Arg51Gly),presenting with bilateral microphthalmia with iris-choroidal coloboma and flexion of joints.The mother carried the same heterozygous variant but had a normal phenotype.Proband 2 carried the unreported variant c.1042G>T/p.(Glu348*),manifesting as left-sided microphthalmia with a normal right eye and no other systemic abnormalities.Through literature review,we found that under a dominant inheritance pattern,80%of heterozygous pathogenic MAB21L2 variants(20/25)and 100%of heterozygous pathogenic MAB21L1 variants(25/25)occurred in the amino acid region 49-52,resulting in microphthalmia,anophthalmia,and coloboma(MAC).Some patients with heterozygous MAB21L2 variants in this region exhibited additional skeletal and joint dysplasia(12/24,50%).Heterozygous truncating variants in MAB21L2 led to MAC(5/5,100%),while those in MAB21L1 were non-pathogenic.Conclusions:This study identified a novel pathogenic variant and a known hotspot pathogenic variant of MAB21L2 in two families with microphthalmia.Through a comprehensive literature review,we compared and summarized the mutation spectrums and genotype-phenotype correlations of MAB21L1 and MAB21L2 genes,providing valuable insights for the diagnosis and differential diagnosis of genetic diseases caused by these gene defects.

关 键 词：先天性小眼球 MAB21L2基因 MAB21L1基因 突变热点 

分 类 号：R77[医药卫生—眼科]