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CASE REPORT article

Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 12 - 2024 | doi: 10.3389/fped.2024.1503455

Prenatal diagnosis of novel compound heterozygous variants in WDR35 gene causing short-rib thoracic dysplasia 7 with or without polydactyly (SRTD7)

Provisionally accepted
Jianlong Zhuang Jianlong Zhuang 1*Junyu Wang Junyu Wang 1Zhengping Huang Zhengping Huang 2Chen Yu'e Chen Yu'e 1Chunnuan Chen Chunnuan Chen 2
  • 1 Center for Prenatal Diagnosis, Quanzhou Women's and Children's Hospital, Quanzhou, China
  • 2 The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

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

    Background: Whole exome sequencing (WES) technology has been increasingly used for the etiological diagnosis of fetuses with ultrasound anomalies. In this article, we report a novel deletion compound combined with a causative variant in WDR35 gene leading to short-rib thoracic dysplasia 7 (SRTD7) with or without polydactyly using WES.: This study involved a Chinese fetus with clinical features of skeletal dysplasia on ultrasound imaging, in whom chromosome abnormalities and copy number variants (CNVs) were detected by chromosomal microarray analysis (CMA), and sequence variants were detected by WES. The obtained results were further verified by Sanger sequencing or qPCR. Results: No chromosomal abnormality or CNVs were identified in the fetus by CMA. However, WES result revealed a 14.38-Kb large novel deletion compound covering exon 7 to exon 12 combined with a missense variant NM_001006657.2:c.932G>T(p.W311L) in WDR35. Both variants were thought of as pathogenic, which was further confirmed by Sanger sequencing and qPCR. In addition, two compound heterozygous variants NM_015102.5:c.[1196A>G(p.E399G)];[1972C>T(p.R658*)] in NPHP4 gene were also identified in the fetus, which may be partially responsible for fetal kidney hyperechogenicity and oligohydramnios.This is the first study reporting a novel deletion compound combined with a causative missense variant in WDR35 leading to SRTD7. This finding may broaden the spectrum of variants of WDR35 gene and provide a valuable reference for clinical counseling of related abnormalities in pregnancies.

    Keywords: whole exome sequencing, Chromosomal microarray analysis, WDR35, NPHP4, Etiology diagnosis

    Received: 29 Sep 2024; Accepted: 24 Dec 2024.

    Copyright: © 2024 Zhuang, Wang, Huang, Yu'e and Chen. 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: Jianlong Zhuang, Center for Prenatal Diagnosis, Quanzhou Women's and Children's Hospital, Quanzhou, 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.