两个不相关的土耳其家庭中与糖原贮积病VI型相关的新型剪接位点突变的鉴定与特征分析
Identification and Characterization of a Novel Splice Site Mutation Associated with Glycogen Storage Disease Type VI in Two Unrelated Turkish Families.
作者信息
Grünert Sarah C, Hannibal Luciana, Schumann Anke, Rosenbaum-Fabian Stefanie, Beck-Wödl Stefanie, Haack Tobias B, Grimmel Mona, Bertrand Miriam, Spiekerkoetter Ute
机构信息
Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre University of Freiburg, 79106 Freiburg, Germany.
Laboratory of Clinical Biochemistry and Metabolism, Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany.
出版信息
Diagnostics (Basel). 2021 Mar 12;11(3):500. doi: 10.3390/diagnostics11030500.
INTRODUCTION
Glycogen storage disease type VI (GSD VI) is a disorder of glycogen metabolism due to mutations in the gene. Patients with GSD VI usually present with hepatomegaly, recurrent hypoglycemia, and short stature.
RESULTS
We report on two non-related Turkish patients with a novel homozygous splice site variant, c.345G>A, which was shown to lead to exon 2 skipping of the PYGL-mRNA by exome and transcriptome analysis. According to an in silico analysis, deletion Arg82_Gln115del is predicted to impair protein stability and possibly AMP binding.
CONCLUSION
GSD VI is a possibly underdiagnosed disorder, and in the era of next generation sequencing, more and more patients with variants of unknown significance in the -gene will be identified. Techniques, such as transcriptome analysis, are important tools to confirm the pathogenicity and to determine therapeutic measures based on genetic results.
引言
糖原贮积病VI型（GSD VI）是一种由于基因发生突变导致的糖原代谢紊乱疾病。GSD VI患者通常表现为肝肿大、反复低血糖和身材矮小。
结果
我们报告了两名无关的土耳其患者，他们携带一种新的纯合剪接位点变异c.345G>A，通过外显子组和转录组分析表明该变异导致PYGL - mRNA外显子2跳跃。根据计算机分析，预测缺失Arg82_Gln115del会损害蛋白质稳定性并可能影响AMP结合。
结论
GSD VI可能是一种诊断不足的疾病，在下一代测序时代，将会鉴定出越来越多携带该基因中意义未明变异的患者。转录组分析等技术是确认致病性并根据基因结果确定治疗措施的重要工具。
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