Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands.

IF 0.9 4区医学 Q4 GENETICS & HEREDITY

Molecular Syndromology Pub Date : 2023-08-01 Epub Date: 2023-06-08 DOI:10.1159/000530256

Lisca Florence Wurfbain, Inge Lucia Cox, Maria Francisca van Dooren, Augusta Maria Antonia Lachmeijer, Virginie Johanna Maria Verhoeven, Johanna Maria van Hagen, Malou Heijligers, Jolien Sietske Klein Wassink-Ruiter, Saskia Koene, Saskia Mariska Maas, Hermine Elisabeth Veenstra-Knol, Johannes Kristian Ploos van Amstel, Maarten Pieter Gerrit Massink, Aebele Barber Mink van der Molen, Marie-José Henriette van den Boogaard

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引用次数: 0

Abstract

Objectives: Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA/P cases.

Methods: Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA/P phenotypes was performed in 212 unrelated CLA/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated.

Results: In 24 CLA/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES).

Conclusion: This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families.

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荷兰唇裂、齿槽裂和/或腭裂（非）综合征患者的诊断性基因组检测。

目的：唇裂、齿槽裂和/或腭裂（CLA/P）是人类最常见的颅面先天畸形。这些口腔裂隙可分为非综合征（孤立的）和综合征形式。许多与口裂相关的综合征临床表现各异，遗传基因也不尽相同，因此很难区分综合征与非综合征病例。识别综合征/遗传原因对于个性化定制护理、识别（未识别的）合并症和准确的遗传咨询非常重要。因此，在 CLA/P 患者的诊断中，越来越多地采用基于新一代测序（NGS）的靶向基因组检测。在这项回顾性研究中，我们评估了在一组 CLA/P 病例中进行 NGS 基因组检测的结果：方法：2015 年至 2020 年期间，我们对 212 名接受遗传咨询后的非亲属关系 CLA/P 患者进行了全外显子组测序（WES），随后对事先选定的一组与 CLA/P 表型相关的基因进行了变异检测和解读。对包括家族史和其他基因检测结果在内的医疗记录进行了评估：结果：在 24 例 CLA/P 患者（11.3%）中发现了致病基因变异。在这 24 例中，有 20 例患有遗传综合征，需要进行专门的监测和随访。在这 24 个病例中，有 6 个（25%）在检测前被推测为孤立的 CLA/P 病例，占总数的 2.8%。8 例 CLA/P 病例（3.8%）在基于 NGS 的基因面板检测后未确诊，但通过其他基因分析（如 SNP 阵列、单基因检测、三重 WES）确定了分子诊断：本研究表明，在 CLA/P 患者的诊断工作中，基于 NGS 的基因组检测是一种强有力的诊断工具。此外，在明显孤立的病例和非家族病例中，也能确定基因诊断。早期诊断有助于为患者提供个性化治疗，并为其家庭提供准确的遗传咨询。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.