首页|应用Minigene剪接变异体分析技术诊断PMM2基因非经典剪接位点新变异的致病性

应用Minigene剪接变异体分析技术诊断PMM2基因非经典剪接位点新变异的致病性

扫码查看
目的:研究Minigene剪接变异体分析技术在诊断磷酸甘露糖变位酶2(PMM2)相关先天性糖基化障碍(PMM2-CDG)中的价值,探讨磷酸甘露糖变位酶2(PMM2)基因剪接位点新变异对其转录产物的影响.方法:通过对1 例PMM2-CDG患儿进行高通量测序查找可能的遗传学病因,利用Minigene剪接变异体分析技术,研究PMM2基因新剪接位点变异的致病性.根据美国医学遗传学与基因组学学会(ACMG)指南,判断新变异的致病性.结果:遗传学分析发现患儿系PMM2 基因母源性c.691G>A(p.Val231Met)变异和父源性c.447+5G>A变异复合杂合子.Minigene剪接变异体分析发现:变异c.447+5G>A导致PMM2 基因转录产物形成r.348_447del转录本,为致病性PMM2 基因变异.患儿的临床特征为皮肤巩膜黄染,血清总胆红素、非结合胆红素和总胆汁酸明显升高,白蛋白明显降低,甲胎蛋白、铁蛋白和促甲状腺素等升高,对症支持治疗效果欠佳.结论:Minigene剪接变异体分析可为PMM2-CDG确诊和家系遗传咨询提供新的分子标记物,扩展了PMM2 基因变异谱,为该病的临床诊治提供新的参考依据.
Application of minigene splicing variant analysis to diagnose the pathogenicity of a novel non-canonical splicing-site variant of the PMM2 gene
Objective:To investigate the value of minigene splicing variant analysis in the diagnosis of phosphomannomutase 2-congenital disorder of glycosylation(PMM2-CDG),and to explore the impact of a novel splicing-site variant on the transcript products of the PMM2 gene.Methods:High-throughput sequencing was performed on a PMM2-CDG patient to identify the genetic etiology.Minigene splicing variant analysis was performed to explore the pathogenicity of a novel splicing-site variant in the PMM2 gene.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the pathogenicity of the novel variant was determined.Results:On genetic analysis,the patient was a compound heterozygote of the maternal c.691G>A(p.Val231Met)and the paternal c.447+5G>A variants of the PMM2 gene.On minigene splicing variant analysis,the c.447+5G>A variant resulted in the formation of the aberrant transcript r.348_447del,indicating a pathogenic PMM2 variant.The clinical features of the patient were jaundice of the skin and sclera.The serum total bilirubin,unconjugated bilirubin,and total bile acids were significantly increased,albumin was significantly decreased,while alpha-fetoprotein,ferritin and thyrotropin were elevated.Symptomatic and supportive therapy was given,but the effect was not promising.Conclusion:Minigene splicing variant analysis revealed a new molecular marker for the definitive diagnosis and familial genetic counseling of PMM2-CDG,expanded the PMM2 genetic variant spectrum,and provided laboratory evidences for the clinical diagnosis and treatment of this condition.

PMM2 genephosphomannomutase 2-congenital disorder of glycosylation(PMM2-CDG)minigene splicing variant analysis

周琴、林伟霞、宋元宗

展开 >

暨南大学 附属第一医院 儿科,广东 广州 510630

磷酸甘露糖变位酶2(PMM2)基因 PMM2相关先天性糖基化障碍(PMM2-CDG) Minigene剪接变异体分析

广东省基础与应用基础研究基金广州市科技计划广州市科技计划暨南大学附属第一医院临床前沿新技术立项项目

2021A15151110832022010200882023A03J1010JNU1AF-CFTP2022-a01228

2024

暨南大学学报(自然科学与医学版)
暨南大学

暨南大学学报(自然科学与医学版)

CSTPCD北大核心
影响因子:0.996
ISSN:1000-9965
年,卷(期):2024.45(2)