Expanding the Genetic Spectrum of AGXT Gene Variants in Egyptian Patients with Primary Hyperoxaluria Type I.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Somayya Naguib, Lamiaa A Mansour, Neveen A. Soliman, Hadeel M El-Hanafy, Y. Fahmy, M. Elmonem, Radwa M Abdel Halim
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Abstract

Introduction: Approximately 80% of primary hyperoxaluria cases are caused by primary hyperoxaluria type 1 (PH1, OMIM# 259900), which is characterized by pathogenic variants in the AGXT gene, resulting in deficiency of the liver-specific enzyme alanine-glyoxylate aminotransferase (AGT). This leads to increased production of oxalate, which cannot be effectively eliminated from the body, resulting in its accumulation primarily in the kidneys and other organs. Subjects and Methods: This study included 17 PH1 Egyptian patients from 12 unrelated families, recruited from the Inherited Kidney Disease Outpatient Clinic and the Dialysis Units, Cairo University Hospitals, during the period from January 2018 to December 2019, aiming to identify the pathogenic variants in the AGXT gene. Results: Six different variants were detected. These included three frameshift and three missense variants, all found in homozygosity within the respective families. The most common variant was c.121G>A;p.(Gly41Arg) detected in four families, followed by c.725dup;p.(Asp243GlyfsTer12) in three families, c.33dup;p.(Lys12Glnfs156) in two families, and c.731T >C;p.(Ile244Thr), c.33delC;p.(Lys12Argfs34), and c.568G>A;p.(Gly190Arg) detected in one family each. Conclusion: Consanguineous Egyptian families with history of renal stones or renal disease suspicious of primary hyperoxaluria should undergo AGXT genetic sequencing, specifically targeting exons 1 and 7, as variants in these two exons account for >75% of disease-causing variants in Egyptian patients with confirmed PH1.
扩大埃及原发性高草酸尿症 I 型患者 AGXT 基因变异的遗传范围。
简介大约 80% 的原发性高草酸尿症病例是由原发性高草酸尿症 1 型(PH1,OMIM# 259900)引起的,其特点是 AGXT 基因的致病变异导致肝脏特异性酶丙氨酸-乙醛酸氨基转移酶(AGT)缺乏。这导致草酸盐的生成量增加,而草酸盐无法有效排出体外,主要在肾脏和其他器官中积聚。研究对象和方法:本研究纳入了 2018 年 1 月至 2019 年 12 月期间从开罗大学医院遗传性肾病门诊和透析室招募的来自 12 个非亲缘家庭的 17 名 PH1 埃及患者,旨在确定 AGXT 基因中的致病变体。结果:共检测到六种不同的变异。其中包括三个框移位变异和三个错义变异,所有变异均在相应的家族中以同源性发现。最常见的变异是在四个家族中检测到的 c.121G>A;p.(Gly41Arg),其次是在三个家族中检测到的 c.725dup;p.(Asp243GlyfsTer12),再次是在三个家族中检测到的 c.33dup;p.(Lys12)。c.731T>C;p.(Ile244Thr)、c.33delC;p.(Lys12Argfs34)和 c.568G>A;p.(Gly190Arg)。结论有肾结石或肾脏疾病史的埃及近亲家族如怀疑患有原发性高草酸尿症,应进行 AGXT 基因测序,特别是针对 1 号和 7 号外显子,因为这两个外显子上的变异占埃及 PH1 确诊患者致病变异的 75% 以上。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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