Genetic Findings in Short Turkish Children Born to Consanguineous Parents.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Sjoerd D Joustra, Emregul Isik, Jan M Wit, Gonul Catli, Ahmet Anik, Belma Haliloglu, Nurgun Kandemir, Elif Ozsu, Yvonne M C Hendriks, Christiaan de Bruin, Sarina G Kant, Angel Campos-Barros, Rachel C Challis, David Parry, Margaret E Harley, Andrew Jackson, Monique Losekoot, Hermine A van Duyvenvoorde
{"title":"Genetic Findings in Short Turkish Children Born to Consanguineous Parents.","authors":"Sjoerd D Joustra, Emregul Isik, Jan M Wit, Gonul Catli, Ahmet Anik, Belma Haliloglu, Nurgun Kandemir, Elif Ozsu, Yvonne M C Hendriks, Christiaan de Bruin, Sarina G Kant, Angel Campos-Barros, Rachel C Challis, David Parry, Margaret E Harley, Andrew Jackson, Monique Losekoot, Hermine A van Duyvenvoorde","doi":"10.1159/000539696","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented.</p><p><strong>Methods: </strong>This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height &lt;-3.5 standard deviation score [SDS]) and microcephaly (head circumference &lt;-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c).</p><p><strong>Results: </strong>In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively.</p><p><strong>Conclusion: </strong>Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616538/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormone Research in Paediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000539696","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented.

Methods: This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height <-3.5 standard deviation score [SDS]) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c).

Results: In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively.

Conclusion: Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.

近亲结婚的土耳其矮小儿童的遗传学发现。
引言 在评估身材矮小儿童时,基因分析的诊断率取决于相关的临床特征,但父母近亲结婚的额外影响尚未得到充分证实。方法 本观察性病例系列由六个儿科内分泌学转诊中心收集,涉及 34 个近亲结婚家庭的 42 名矮小儿童(纳入标准:身材矮小和父母近亲结婚)。在 18 名患者(12 个家庭,第 1 组)中,临床特征表明生长激素(GH)-胰岛素样生长因子 I(IGF-I)轴存在特定遗传缺陷,因此采用了候选基因方法。其他患者(第 2 组)则选择了无假设方法(基因面板、芯片分析和全外显子组测序),并进一步细分为 11 例严重矮身材(身高 <-3.5SDS)和小头畸形(头围 <-3.0SDS)患者(第 2a 组)、10 例综合征矮身材患者(第 2b 组)和 3 例非特异性孤立 GH 缺乏症患者(第 2c 组)。结果 在第 1 组的所有 12 个家庭中,发现了 GHR、IGFALS、GH1 和 STAT5B(可能)致病变体。在第 2a 组的 9/12 个家庭中,检测到 PCNT、SMARCAL1、SRCAP、WDR4 和 GHSR 变异。在 2b 组的 5/9 个家庭中,发现了 TTC37、SCUBE3、NSD2、RABGAP1 和 17p13.3 微缺失变异。在 2c 组中,没有发现遗传原因。在 21、1 和 4 名患者中分别发现了同卵、复合杂合和杂合变异。结论 对父母为近亲的矮小儿童进行基因检测具有很高的诊断率,尤其是对严重 GH 缺乏或不敏感、小头畸形和综合征性矮身材的病例。
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
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
×
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