ATP7B Gene Variant Profile İdentified by NGS in Wilson's Disease.

IF 0.7 4区医学 Q4 PATHOLOGY

Fetal and Pediatric Pathology Pub Date : 2023-12-01 Epub Date: 2023-11-22 DOI:10.1080/15513815.2023.2260005

Orhan Gorukmez, Taner Özgür, Ozlem Gorukmez, Ali Topak

{"title":"ATP7B Gene Variant Profile İdentified by NGS in Wilson's Disease.","authors":"Orhan Gorukmez, Taner Özgür, Ozlem Gorukmez, Ali Topak","doi":"10.1080/15513815.2023.2260005","DOIUrl":null,"url":null,"abstract":"Background: Wilson's disease (WD) is a copper metabolism disorder caused by ATP7B gene mutations and shows an autosomal recessive pattern of inheritance. We aimed to contribute to the mutation profile of ATP7B and show demographic and phenotypic differences in this study. Materials and methods: The clinical and demographic characteristics of patients who underwent ATP7B gene sequence analysis using next-generation sequencing were evaluated to improve genotype-phenotype correlation in WD. Results: An uncertain significance (D563N) and seven likely pathogenic (Y532D, Y715Y, T977K, K1028*, E1086K, A1227Pfs*103, and E1242K) variants were identified as associated with WD. Uniparental disomy was detected in one case. Conclusion: Our work expanded the ATP7B variant spectrum and pointed to clinical heterogeneity in ATP7B variants among patients with WD. All symptomatic patients had hepatic involvement and were clinically and/or genetically diagnosed with WD in the pediatric period. T977K, A1003V, H1069Q, E1086K, and N1270S variants were associated with hepatic failure.","PeriodicalId":50452,"journal":{"name":"Fetal and Pediatric Pathology","volume":" ","pages":"891-900"},"PeriodicalIF":0.7000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fetal and Pediatric Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15513815.2023.2260005","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/22 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Wilson's disease (WD) is a copper metabolism disorder caused by ATP7B gene mutations and shows an autosomal recessive pattern of inheritance. We aimed to contribute to the mutation profile of ATP7B and show demographic and phenotypic differences in this study. Materials and methods: The clinical and demographic characteristics of patients who underwent ATP7B gene sequence analysis using next-generation sequencing were evaluated to improve genotype-phenotype correlation in WD. Results: An uncertain significance (D563N) and seven likely pathogenic (Y532D, Y715Y, T977K, K1028*, E1086K, A1227Pfs*103, and E1242K) variants were identified as associated with WD. Uniparental disomy was detected in one case. Conclusion: Our work expanded the ATP7B variant spectrum and pointed to clinical heterogeneity in ATP7B variants among patients with WD. All symptomatic patients had hepatic involvement and were clinically and/or genetically diagnosed with WD in the pediatric period. T977K, A1003V, H1069Q, E1086K, and N1270S variants were associated with hepatic failure.

查看原文本刊更多论文

NGS鉴定Wilson病ATP7B基因变异图谱。

背景：Wilson病（WD）是一种由ATP7B基因突变引起的铜代谢紊乱，表现为常染色体隐性遗传。我们的目的是为ATP7B的突变谱做出贡献，并在本研究中显示人口统计学和表型差异。材料和方法：评估使用下一代测序进行ATP7B基因序列分析的患者的临床和人口统计学特征，以改善WD的基因型-表型相关性。结果：一个不确定的显著性（D563N）和七个可能的致病性（Y532D、Y715Y、T977K、K1028*、E1086K、A1227Pfs*103和E1242K）变体被鉴定为与WD相关。在一个案例中发现了单亲精神错乱。结论：我们的工作扩展了ATP7B变体谱，并指出WD患者ATP7B变异的临床异质性。所有有症状的患者都有肝脏受累，并且在儿科时期被临床和/或遗传诊断为WD。T977K、A1003V、H1069Q、E1086K和N1270S变体与肝衰竭相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Fetal and Pediatric Pathology 医学-病理学

CiteScore

3.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Fetal and Pediatric Pathology is an established bimonthly international journal that publishes data on diseases of the developing embryo, newborns, children, and adolescents. The journal publishes original and review articles and reportable case reports. The expanded scope of the journal encompasses molecular basis of genetic disorders; molecular basis of diseases that lead to implantation failures; molecular basis of abnormal placentation; placentology and molecular basis of habitual abortion; intrauterine development and molecular basis of embryonic death; pathogenisis and etiologic factors involved in sudden infant death syndrome; the underlying molecular basis, and pathogenesis of diseases that lead to morbidity and mortality in newborns; prenatal, perinatal, and pediatric diseases and molecular basis of diseases of childhood including solid tumors and tumors of the hematopoietic system; and experimental and molecular pathology.