划定东亚人与 PIK3CA 相关的过度生长谱系的表型和基因型。

IF 2.3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hongrui Chen, Bin Sun, Hongyuan Liu, Wei Gao, Yajing Qiu, Chen Hua, Xiaoxi Lin
{"title":"划定东亚人与 PIK3CA 相关的过度生长谱系的表型和基因型。","authors":"Hongrui Chen, Bin Sun, Hongyuan Liu, Wei Gao, Yajing Qiu, Chen Hua, Xiaoxi Lin","doi":"10.1007/s00438-024-02159-w","DOIUrl":null,"url":null,"abstract":"<p><p>PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.\",\"authors\":\"Hongrui Chen, Bin Sun, Hongyuan Liu, Wei Gao, Yajing Qiu, Chen Hua, Xiaoxi Lin\",\"doi\":\"10.1007/s00438-024-02159-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.</p>\",\"PeriodicalId\":18816,\"journal\":{\"name\":\"Molecular Genetics and Genomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Genetics and Genomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s00438-024-02159-w\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics and Genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00438-024-02159-w","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

PIK3CA相关发育过度谱(PROS)是一个总称,用来描述一系列不同的发育障碍。迄今为止,相关研究主要集中在欧洲和北美地区,而针对东亚人群的研究则十分稀少。目前,东亚人群中 PIK3CA 变体在不同基因位点上的发生率和分布及其与不同表型的相关性仍不清楚。本研究旨在阐明东亚人群中 PROS 的表型与基因型的相关性。我们展示了 82 名中国患者的表型和基因型。在我们的队列中,67人携带PIK3CA变异,包括错义、框移和剪接变异。6名患者同时携带PIK3CA和另外一种变体。七名PIK3CA阴性患者的PROS表现与GNAQ、AKT1、PTEN、MAP3K3、GNA11或KRAS中的变异重叠。对东亚人群相关文献的综合回顾显示,特定变异与某些 PROS 表型有着独特的关联。在巨脑症和伴有过度生长的弥漫性毛细血管畸形病例中,只发现了一些罕见变异。在中枢神经系统表型中,具有未确定致癌性的非热点变异更为常见。伴有血管畸形的疾病更有可能出现螺旋结构域的变异,而不伴有血管异常的脂肪/肌肉过度生长表型则主要出现C2结构域的变异。我们的研究结果强调了东亚 PROS 群体中独特的表型-基因型模式,突出了扩大群体以进一步阐明这些相关性的必要性。这些努力将极大地促进未来为东亚人群量身定制的 PI3Kα 选择性抑制剂的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.

Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

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
Molecular Genetics and Genomics
Molecular Genetics and Genomics 生物-生化与分子生物学
CiteScore
5.10
自引率
3.20%
发文量
134
审稿时长
1 months
期刊介绍: Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. Any approach to the study of genes and genomes is considered, be it experimental, theoretical or synthetic. MGG publishes research on all organisms that is of broad interest to those working in the fields of genetics, genomics, biology, medicine and biotechnology. The journal investigates a broad range of topics, including these from recent issues: mechanisms for extending longevity in a variety of organisms; screening of yeast metal homeostasis genes involved in mitochondrial functions; molecular mapping of cultivar-specific avirulence genes in the rice blast fungus and more.
×
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