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.
先天性小眼畸形是一种罕见的先天性眼球发育异常，表现为眼球体积缩小和结构紊乱，常伴有眼组织缺损，严重影响患者的视觉功能。该病可单独发生，仅影响眼部，也可作为全身综合征的表现之一，同时伴有全身多器官或系统的异常。目前已发现82个先天性小眼畸形致病基因，能解释近2/3患者的发病原因。MAB21L1和MAB21L2是高度同源的两个基因，两者的致病变异均可导致小眼畸形，但又各自存在独特的表型特征。本期封面文章报道了MAB21L2基因变异导致小眼畸形2例，并通过回顾文献绘制变异频谱，从变异热点、变异类型、表型特征和基因型-表型相互关系等方面，对MAB21L1和MAB21L2进行比较，为两者缺陷所致眼遗传病的鉴别和诊断提供依据。
先天性小眼畸形是一种罕见的先天性眼球发育异常，表现为眼球体积缩小和结构紊乱，常伴有眼组织缺损，严重影响患者的视觉功能。该病可单独发生，仅影响眼部，也可作为全身综合征的表现之一，同时伴有全身多器官或系统的异常。目前已发现82个先天性小眼畸形致病基因，能解释近2/3患者的发病原因。MAB21L1和MAB21L2是高度同源的两个基因，两者的致病变异均可导致小眼畸形，但又各自存在独特的表型特征。本期封面文章报道了MAB21L2基因变异导致小眼畸形2例，并通过回顾文献绘制变异频谱，从变异热点、变异类型、表型特征和基因型-表型相互关系等方面，对MAB21L1和MAB21L2进行比较，为两者缺陷所致眼遗传病的鉴别和诊断提供依据。
目的：利用信息化手段，优化眼遗传病患者的随访途径，降低病历资料缺失率，助力临床检验科室高效运营。方法：通过态势分析法搜集需求，基于微信公众号平台“中山大学眼科医院小儿遗传”，搭建眼遗传病信息管理系统。根据是否使用眼遗传病信息管理系统、是否受到人员流动限制，将2017年7月1日—2023年11月30日来院进行基因检测的患者分为四组：传统组、传统+人流限制组、微信组和微信+人流限制组，通过χ2检验对眼遗传病信息管理系统进行性能评价。结果：源软件架设在阿里云电子政务平台的眼遗传病信息管理系统，通过加密通讯与医院网络交互。系统主要分为基因检测业务、数据管理和系统管理三大模块。使用该系统的患者或亲属可以在任意时间和地点，自主上传病历资料、签署知情同意书、查询基因检测报告，如有需要还能进行一对一的沟通实现长期随访。在此过程中，患者的临床信息实现数字化。研究共纳入10 662例患者对该系统进行性能评价，使用眼遗传病信息管理系统后，患者病历资料缺失率显著降低，由12.2%(传统+人流限制组)降至2.7%(微信+人流限制组)；患者二次来访率由最高的70%(传统组)降至最低的11.7%(微信组)；两类比较差异有统计学意义(P<0.001)。结论：眼遗传病信息管理系统的使用显著降低患者病历资料缺失率和眼遗传病患者的二次来访率。
Objective: To optimize the follow-up approach for patients with ophthalmic genetic diseases through informational technology, reduce the loss rate of cases, and facilitate the efficient operation of the clinical laboratory. Methods: Using the SWOT analysis method to collect requirements, ‘Pediatric Genetics of Zhongshan Ophthalmic Center’, an ophthalmic genetics information management system for ophthalmic genetic diseases was established on the Wechat public platform. Based on whether the ophthalmic genetic disease information management system was used and there were personnel mobility restrictions, patients who underwent genetic testing in the hospital for genetic testing from July 1, 2017, to November 30, 2023, were divided into four groups: traditional group, traditional+ lockdown group, Wechat+ lockdown group, and Wechat group. Te chi-square test was used to evaluate the performance of the ophthalmic genetic information management system. Results:The ophthalmic genetic disease information management system, which is based on open-source sofware and hosted on the Alibaba Cloud e-government platform, interacts with the hospital network through encrypted communication. Te system was divided into three modules: gene detection business, data management, and system management. By the system, patients or relatives can upload medical records, sign informed consent, inquire about genetic test reports at any time and anywhere, and conduct one-on-one communication to achieve long-term follow-up if necessary. In this process, the patient's clinical information was digitized. A total of 10,662 patients were included in the study to evaluate the performance of the system. The loss rate of cases was decreased from 12.2%to 2.7%, and the rate of second visits was reduced from 70% to 11.7%, which were statistically different, respectively (P< 0.001). Conclusion: Te application of the ophthalmic genetic information management system has signifcantly reduced the loss rate of cases and the rate of second visits in patients with ophthalmic genetic diseases.
