Skip to main content

ORIGINAL RESEARCH article

Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 12 - 2024 | doi: 10.3389/fped.2024.1429586

Novel loss-of-function variants in WDR26 cause Skraban-Deardorff syndrome in two Chinese patients

Provisionally accepted
Qi Yang Qi Yang Xunzhao Zhou Xunzhao Zhou Sheng Yi Sheng Yi Xiaoling Li Xiaoling Li Qiang Zhang Qiang Zhang Shujie Zhang Shujie Zhang Li Lin Li Lin Shang Yi Shang Yi Biyan Chen Biyan Chen Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo *
  • Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China

The final, formatted version of the article will be published soon.

    Mutations in the protein WD repeat structural domain 26 (WDR26, MIM 617424) have been identified as the cause of autosomal dominant Skraban-Deardorff syndrome, a rare genetic disorder characterized by intellectual disability (ID), developmental delay (DD), hypotonia, epilepsy, infant feeding difficulties, gait abnormalities and distinctive facial features. The objective of this study is to investigate the genetic factors that may contribute to the development of Skraban-Deardorff syndrome in affected individuals.In this study, we used whole-exome sequencing (WES) to analyze pathogenic and likely pathogenic variants in two unrelated Chinese patients with DD and ID. We confirmed the origin of the variants by conducting Sanger sequencing and classified them according to ACMG/AMP guidelines.Here, two novel de novo variants (c.1797delC(p.His599fs*11) and c.1414C>T(p.Gln472*)) in the WDR26 gene have been identified in two Chinese patients with Skraban-Deardorff syndrome. These patients exhibit a range of symptoms, including varying degrees of ID, DD, speech delay, an abnormal wide-foot and/or stiff-legged gait, facial dysmorphism, behavioural abnormalities, with or without seizures.In this study, We report two unrelated Chinese patients with Skraban-Deardorff syndrome caused by novel de novo pathogenic variants of the WDR26 gene. These patients showed a clinical phenotype similar to that of patients with the WDR26 variant. Compared to reported cases with WDR26 pathogenic variants, patient 2 presented a novel complication of severe behavioural problems, including hyperactivity, social anxiety, self-mutilation, impulsivity and violent behaviour. This research broadens the range of genetic and clinical features of Skraban-Deardorff syndrome. In addition, the symptoms may become more pronounced as the patient ages. Furthermore, our report highlights the clinical diversity of Skraban-Deardorff syndrome. The findings may assist healthcare professionals in providing more accurate genetic testing and counselling to affected families and improving the overall management of the condition.

    Keywords: Novel de novo variants, WDR26, Skraban-Deardorff Syndrome, Intellectual Disability, developmental delay, hypotonia, Behavioural problems, Seizures

    Received: 08 May 2024; Accepted: 06 Sep 2024.

    Copyright: © 2024 Yang, Zhou, Yi, Li, Zhang, Zhang, Lin, Yi, Chen, Qin and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jingsi Luo, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.