Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays.

IF 2.3 3区医学 Q2 GENETICS & HEREDITY

Clinical Genetics Pub Date : 2025-06-30 DOI:10.1111/cge.14781

Etienne Bizot, Dima Jouni, Caroline Rooryck, Juliet Taylor, Marine Legendre, Lorelei Charbonnier, Julia Metreau, Emmanuelle Benaloun, Audrey Pinson, Geneviève Quenum, Jérôme Bouligand, Gérard Tachdjian, Philippe Labrune, Lucie Tosca

{"title":"Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays.","authors":"Etienne Bizot, Dima Jouni, Caroline Rooryck, Juliet Taylor, Marine Legendre, Lorelei Charbonnier, Julia Metreau, Emmanuelle Benaloun, Audrey Pinson, Geneviève Quenum, Jérôme Bouligand, Gérard Tachdjian, Philippe Labrune, Lucie Tosca","doi":"10.1111/cge.14781","DOIUrl":null,"url":null,"abstract":"<p><p>To date, only one study describes three unrelated cases of neurodevelopmental disorders associated with duplications in 22q13.2, which include the TCF20 gene. In contrast, TCF20 variants and deletions are well characterized. Here, we report six new cases of 22q13.2 gain, including TCF20, identified through array-comparative genomic hybridization (array-CGH). Probands exhibited neurodevelopmental delay, and several presented with facial dysmorphism, abnormal growth parameters, and abnormalities affecting the skeletal, respiratory, genitourinary, and/or cardiovascular systems. We documented one 440 Kb triplication and five cases of duplication ranging from 82.5 Kb to 3.03 Mb in size. Co-segregation analysis of the CNV and clinical symptoms supports variable expressivity. However, the complete penetrance of these gains remains questionable compared to the known pathogenic variants and structural variations associated with loss of function. We discuss the genotype-phenotype correlations and hypotheses surrounding the impairment of TCF20 protein function.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.14781","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

To date, only one study describes three unrelated cases of neurodevelopmental disorders associated with duplications in 22q13.2, which include the TCF20 gene. In contrast, TCF20 variants and deletions are well characterized. Here, we report six new cases of 22q13.2 gain, including TCF20, identified through array-comparative genomic hybridization (array-CGH). Probands exhibited neurodevelopmental delay, and several presented with facial dysmorphism, abnormal growth parameters, and abnormalities affecting the skeletal, respiratory, genitourinary, and/or cardiovascular systems. We documented one 440 Kb triplication and five cases of duplication ranging from 82.5 Kb to 3.03 Mb in size. Co-segregation analysis of the CNV and clinical symptoms supports variable expressivity. However, the complete penetrance of these gains remains questionable compared to the known pathogenic variants and structural variations associated with loss of function. We discuss the genotype-phenotype correlations and hypotheses surrounding the impairment of TCF20 protein function.

查看原文本刊更多论文

包括TFC20在内的6例22q13.2新增病例：首次报道与神经发育迟缓相关的三次重复和最小重复

迄今为止，只有一项研究描述了三例与22q13.2基因重复相关的不相关的神经发育障碍病例，其中包括TCF20基因。相比之下，TCF20的变异和缺失得到了很好的表征。在这里，我们报告了6例新的22q13.2增益，包括TCF20，通过阵列比较基因组杂交（array-CGH）鉴定。先证者表现为神经发育迟缓，一些表现为面部畸形、生长参数异常，以及影响骨骼、呼吸、泌尿生殖系统和/或心血管系统的异常。我们记录了一个440 Kb的复制和五个复制，大小从82.5 Kb到3.03 Mb不等。CNV和临床症状的共分离分析支持可变表达性。然而，与已知的致病变异和与功能丧失相关的结构变异相比，这些增益的完全外显率仍然值得怀疑。我们讨论了围绕TCF20蛋白功能损伤的基因型-表型相关性和假设。

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

Clinical Genetics 医学-遗传学

CiteScore

6.50

自引率

0.00%

发文量

175

审稿时长

3-8 weeks

期刊介绍： Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease