探索 MECP2 靶向测试在实际工作中的临床实用性

IF 3.2 3区 医学 Q2 CLINICAL NEUROLOGY
Soo Yeon Kim MD, PhD , Hyewon Woo MD , Byung Chan Lim MD, PhD , Ki Joong Kim MD, PhD , Jong-Hee Chae MD, PhD
{"title":"探索 MECP2 靶向测试在实际工作中的临床实用性","authors":"Soo Yeon Kim MD, PhD ,&nbsp;Hyewon Woo MD ,&nbsp;Byung Chan Lim MD, PhD ,&nbsp;Ki Joong Kim MD, PhD ,&nbsp;Jong-Hee Chae MD, PhD","doi":"10.1016/j.pediatrneurol.2024.08.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to explore the clinical utility of targeted <em>MECP2</em> testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria.</p></div><div><h3>Methods</h3><p>Eligible participants with global developmental delay/arrest or regression before age 36 months underwent <em>MECP2</em> testing. <em>MECP2</em>-positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age.</p></div><div><h3>Results</h3><p>Of the 683 patients, 162 (23.7%) were diagnosed with <em>MECP2</em>-related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of <em>MECP2</em> testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing.</p></div><div><h3>Conclusions</h3><p>Targeted <em>MECP2</em> testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted <em>MECP2</em> testing in younger patients without typical RTT features.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 28-33"},"PeriodicalIF":3.2000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Clinical Utility of Targeted MECP2 Testing in Real-World Practice\",\"authors\":\"Soo Yeon Kim MD, PhD ,&nbsp;Hyewon Woo MD ,&nbsp;Byung Chan Lim MD, PhD ,&nbsp;Ki Joong Kim MD, PhD ,&nbsp;Jong-Hee Chae MD, PhD\",\"doi\":\"10.1016/j.pediatrneurol.2024.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>This study aimed to explore the clinical utility of targeted <em>MECP2</em> testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria.</p></div><div><h3>Methods</h3><p>Eligible participants with global developmental delay/arrest or regression before age 36 months underwent <em>MECP2</em> testing. <em>MECP2</em>-positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age.</p></div><div><h3>Results</h3><p>Of the 683 patients, 162 (23.7%) were diagnosed with <em>MECP2</em>-related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of <em>MECP2</em> testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing.</p></div><div><h3>Conclusions</h3><p>Targeted <em>MECP2</em> testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted <em>MECP2</em> testing in younger patients without typical RTT features.</p></div>\",\"PeriodicalId\":19956,\"journal\":{\"name\":\"Pediatric neurology\",\"volume\":\"161 \",\"pages\":\"Pages 28-33\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0887899424002856\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0887899424002856","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景本研究旨在对一大批患有神经发育迟缓的女性患者进行有针对性的 MECP2 测试,以探索其临床实用性。我们的目的是根据目前的诊断标准确定合适的检测对象。方法对符合条件的 36 个月前患有全面发育迟缓/停滞或退步的参与者进行 MECP2 检测。根据雷特综合征(RTT)诊断标准,包括典型、非典型、可能和未分类,对MECP2阳性患者进行进一步分类,以评估疾病的典型性和随年龄的进展。约75%的患者在检测时出现发育停滞/退步,最初的主要症状是全身发育迟缓。14名患者(8.6%)在6个月大之前就出现了症状。MECP2测试时的平均年龄为3.7岁,其中31.5%的患者在两岁以下。在两岁以下的患者中,有 15 人最初被归入未分类组,但后来根据随访评估结果,有 12 人被重新归入典型/非典型 RTT 组。在接受监测的超过五岁的 119 名患者中,80% 表现出典型的 RTT 症状,10 人仍未分类,9.8% 存在外显子缺失,这给使用新一代测序技术进行检测带来了挑战。鉴于年轻患者不一定符合典型的 RTT 标准,本研究建议对无典型 RTT 特征的年轻患者进行 MECP2 靶向检测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the Clinical Utility of Targeted MECP2 Testing in Real-World Practice

Background

This study aimed to explore the clinical utility of targeted MECP2 testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria.

Methods

Eligible participants with global developmental delay/arrest or regression before age 36 months underwent MECP2 testing. MECP2-positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age.

Results

Of the 683 patients, 162 (23.7%) were diagnosed with MECP2-related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of MECP2 testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing.

Conclusions

Targeted MECP2 testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted MECP2 testing in younger patients without typical RTT features.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Pediatric neurology
Pediatric neurology 医学-临床神经学
CiteScore
4.80
自引率
2.60%
发文量
176
审稿时长
78 days
期刊介绍: Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信