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CASE REPORT article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1487352

A Novel nonsense mutation in SCAF4 associated with Fliedner-Zweier syndrome: a case report and review of the literature

Provisionally accepted
Zhengfang Chen Zhengfang Chen 1Jing Zhao Jing Zhao 2Xiao Xuan Fan Xiao Xuan Fan 1Xiaoyan Xuan Xiaoyan Xuan 1*Xiaoke Zhao Xiaoke Zhao 1*
  • 1 Department of Rehabilitation, Children’s Hospital of Nanjing Medical University, Nanjing, China
  • 2 Anhui Provincial Children’s Hospital, Hefei, Anhui Province, China

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

    Introduction:Variants in the SR-RELATED C-TERMINAL DOMAIN-ASSOCIATED FACTOR 4 (SCAF4) gene are linked to Fliedner-Zweier syndrome (FZS), which presents with diverse symptoms, including mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. However, there is a paucity of cases describing genotypes and clinical features.We present the case of a four-year and seven-month-old Chinese boy displaying intellectual impairment, language development disorder, behavioral abnormalities, and distinct facial features. Whole exome sequencing (WES) identified a heterozygous nonsense mutation, c.1693C>T (p.Arg565*), located in exon 14 of the SCAF4 gene (NM_020706). Sanger sequencing confirmed paternal inheritance of this mutation. RNA sequencing from the patient demonstrated widespread transcriptional dysregulation, reinforcing the role of SCAF4 dysfunction in impaired transcription and neurodevelopmental disorders. This mutation is novel, not previously recorded in databases such as GnomAD or dbSNP, nor reported in existing literature.We reviewed the clinical features of the patients reported in the literature with mutations in SCAF4 gene and described the case of a Chinese patient with this mutation. This case underscores the critical need for continued exploration of genotype-phenotype correlations, enhancing our understanding of the diverse manifestations of Fliedner-Zweier syndrome and informing future diagnostic and therapeutic strategies.

    Keywords: SCAF4 gene, Fliedner-Zweier syndrome, Neurodevelopmental disorders, WES, RNA sequencing

    Received: 28 Aug 2024; Accepted: 31 Mar 2025.

    Copyright: © 2025 Chen, Zhao, Fan, Xuan and Zhao. 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:
    Xiaoyan Xuan, Department of Rehabilitation, Children’s Hospital of Nanjing Medical University, Nanjing, China
    Xiaoke Zhao, Department of Rehabilitation, Children’s Hospital of Nanjing Medical University, Nanjing, 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.

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