With advances in genetic testing and improved access to such advances, whole exome sequencing is becoming a first‐line investigation in clinical work‐up of children with developmental delay/intellectual disability (ID). As a result, the need to understand the importance of genetic variants and its effect on the clinical phenotype is increasing. Here, we report on the largest cohort of patients with HNRNPU variants. These 21 patients follow on from the previous study published by Yates et al. in 2017 from our group predominantly identified from the Deciphering Developmental Disorders study that reported seven patients with HNRNPU variants. All the probands reported here have a de novo loss‐of‐function variant. These probands have craniofacial dysmorphic features, in the majority including widely spaced teeth, microcephaly, high arched eyebrows, and palpebral fissure abnormalities. Many of the patients in the group also have moderate to severe ID and seizures that tend to start in early childhood. This series has allowed us to define a novel neurodevelopmental syndrome, with a likely mechanism of haploinsufficiency, and expand substantially on already published literature on HNRNPU‐related neurodevelopmental syndrome.

中文翻译：

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21例以前未报告的HNRNPU相关综合征先证者的临床发现，并进行了全面的文献综述。

随着基因测试的进步和对此类进步的获取，全外显子组测序已成为发育迟缓/智力障碍（ID）儿童临床检查的一线研究。结果，越来越需要了解遗传变异的重要性及其对临床表型的影响。在这里，我们报告了HNRNPU变异患者的最大队列。这21位患者来自Yates等人先前发表的研究。2017年，我们小组主要从解密性发育障碍研究中鉴定出该研究，该研究报告了7名HNRNPU变异患者。这里报道的所有先证者都是从头开始的功能丧失型。这些先证者具有颅面畸形的特征，大多数包括宽齿，小头畸形，高弓形眉毛和睑裂异常。该组中的许多患者还具有中度至重度ID和癫痫发作，这种发作往往始于儿童早期。该系列文章使我们能够定义一种新的神经发育综合症，可能具有单倍功能不足的机制，并且在已经发表的有关HNRNPU相关神经发育综合症的文献上有了实质性的扩展。