一个家族的 MEN2 表型与种系杂合子罕见 RET K666N 变异有关。

IF 0.7 Q4 ENDOCRINOLOGY & METABOLISM
A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein
{"title":"一个家族的 MEN2 表型与种系杂合子罕见 RET K666N 变异有关。","authors":"A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein","doi":"10.1530/EDM-24-0009","DOIUrl":null,"url":null,"abstract":"<p><strong>Summary: </strong>Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.</p><p><strong>Learning points: </strong>The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.</p>","PeriodicalId":37467,"journal":{"name":"Endocrinology, Diabetes and Metabolism Case Reports","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378119/pdf/","citationCount":"0","resultStr":"{\"title\":\"MEN2 phenotype in a family with germline heterozygous rare RET K666N variant.\",\"authors\":\"A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein\",\"doi\":\"10.1530/EDM-24-0009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Summary: </strong>Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.</p><p><strong>Learning points: </strong>The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.</p>\",\"PeriodicalId\":37467,\"journal\":{\"name\":\"Endocrinology, Diabetes and Metabolism Case Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378119/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrinology, Diabetes and Metabolism Case Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1530/EDM-24-0009\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinology, Diabetes and Metabolism Case Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1530/EDM-24-0009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"Print","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

摘要:多发性内分泌肿瘤 2 型(MEN2)是一种遗传性癌症综合征,由 RET 原癌基因中的种系激活致病变异引起。MEN2A 是最常见的亚型,有罹患甲状腺髓样癌 (MTC)、嗜铬细胞瘤 (PHEO) 和原发性甲状旁腺功能亢进 (PHPT) 的风险,而 MEN2B 则较少见,与 MTC 和 PHEO 以及粘膜神经瘤有关。人们对特定的RET种系杂合变异体K666N知之甚少。这种变异在极少数家族中出现过,而且在大多数病例中,患者被诊断出的唯一特征是非常不活跃的 MTC。有一例患者同时患有 MTC 和双侧 PHEO。美国甲状腺协会尚未对RET K666N变异型进行分层,有关其致病性的数据也很有限;因此,对无症状的RET K666N携带者进行适当筛查和治疗尚不明确。在此,我们报告了一个具有杂合子生殖系 RET K666N 变异的家庭。原告在一次择期子宫切除术后出现心源性休克和多器官功能衰竭,随后被发现患有PHEO,基因检测发现了RET K666N种系变异。患者的同意是通过 IRB 协议 COMIRB #15-0516.Learning points 获得的:特定的 RET 种系杂合变异 K666N 非常罕见,在极少数家族中也有描述,而且在大多数病例中,患者被诊断出的唯一特征是非常不活跃的 MTC。我们的原告更年轻,患有 PHEO、MTC 和 PHPT。RET K666N种系变异似乎是MEN2的低渗透变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MEN2 phenotype in a family with germline heterozygous rare RET K666N variant.

Summary: Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.

Learning points: The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.

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
CiteScore
1.50
自引率
0.00%
发文量
142
审稿时长
9 weeks
期刊介绍: Endocrinology, Diabetes & Metabolism Case Reports publishes case reports on common and rare conditions in all areas of clinical endocrinology, diabetes and metabolism. Articles should include clear learning points which readers can use to inform medical education or clinical practice. The types of cases of interest to Endocrinology, Diabetes & Metabolism Case Reports include: -Insight into disease pathogenesis or mechanism of therapy - Novel diagnostic procedure - Novel treatment - Unique/unexpected symptoms or presentations of a disease - New disease or syndrome: presentations/diagnosis/management - Unusual effects of medical treatment - Error in diagnosis/pitfalls and caveats
×
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