High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with NLRP7 Pathogenic Variations.

IF 0.5 4区 医学 Q4 GENETICS & HEREDITY
M Kocabey, I Gulhan, A Koc, T Cankaya, V Karatasli, A Ileri
{"title":"High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with <i>NLRP7</i> Pathogenic Variations.","authors":"M Kocabey,&nbsp;I Gulhan,&nbsp;A Koc,&nbsp;T Cankaya,&nbsp;V Karatasli,&nbsp;A Ileri","doi":"10.2478/bjmg-2022-0025","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Pathogenic variations of the <i>NLRP7</i> and <i>KHDC3L</i> genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.</p><p><strong>Material and methods: </strong>Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of <i>NLRP7</i> and <i>KHDC3L</i> genes.</p><p><strong>Results: </strong><i>NLRP7</i> pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the <i>KHDC3L</i> gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.</p><p><strong>Conclusions: </strong>We found that defects of the <i>NLRP7</i> gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/fa/bjmg-25-2-bjmg-2022-0025.PMC10230829.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Balkan Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2478/bjmg-2022-0025","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.

Material and methods: Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes.

Results: NLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.

Conclusions: We found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.

Abstract Image

Abstract Image

具有NLRP7致病变异的复发性包体痣妊娠滋养细胞瘤发展的高风险。
目的:NLRP7和KHDC3L基因的致病变异是家族性复发性葡萄胎的原因,这是一种罕见的常染色体隐性现象,可导致严重的合并症。在不同种族的复发性葡萄胎病例中,遗传缺陷的多样性或疾病进展的自然过程知之甚少。在这项研究中,我们的目的是调查突变谱和妊娠结局的患者多颗磨牙妊娠。材料和方法:本研究包括3例不相关的复发性磨牙妊娠病例。所有患者均无已知的臼齿妊娠家族史。记录临床表现和随访结果。Sanger测序用于揭示NLRP7和KHDC3L基因外显子和外显子-内含子边界的遗传缺陷。结果:3例患者均发现NLRP7致病变异。在两个病例中,鉴定出纯合子c.2471+1G>一个典型剪接引用变异,在一个病例中鉴定出纯合子c.2571dupC (p.Ile858HisfsTer11)移码变异。在任何情况下都没有发现KHDC3L基因的变异。在所有病例中,妊娠滋养细胞瘤的发展使临床过程和治疗方案复杂化。结论:我们发现NLRP7基因的缺陷是我们地区的主要病因,突变谱表明在土耳其人群中存在奠基人效应。我们建议在磨牙妊娠中进行早期遗传诊断和咨询,并建议在转化为妊娠滋养细胞瘤时密切随访。
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
CiteScore
1.00
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Balkan Journal of Medical Genetics is a journal in the English language for publication of articles involving all branches of medical genetics: human cytogenetics, molecular genetics, clinical genetics, immunogenetics, oncogenetics, pharmacogenetics, population genetics, genetic screening and diagnosis of monogenic and polygenic diseases, prenatal and preimplantation genetic diagnosis, genetic counselling, advances in treatment and prevention.
×
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