A novel PRKACB variant associated with bilateral postaxial polydactyly and intrauterine growth restriction: A case report and literature review

Abstract

Objective To characterize the clinical features of a fetus with postaxial polydactyly caused by a de novo PRKACB gene variant and to perform a genetic analysis.

Methods A pregnant woman who presented to Zhejiang Provincial People's Hospital on 4 December 2024 was enrolled in this study. Fetal clinical data were collected, and genomic DNA was extracted from the fetus and both parents. Clinical whole-exome sequencing (WES) was performed on the trio (fetus and both parents). Candidate variants were identified and validated by Sanger sequencing, followed by bioinformatics analysis. This study was approved by the Medical Ethics Committee of Zhejiang Provincial People’s Hospital (approval number: QT2025076).

Results Prenatal ultrasonography revealed bilateral postaxial polydactyly and several fetal biometric measurements that were inconsistent with gestational age. The clinical diagnoses were intrauterine growth restriction and polydactyly. WES identified a de novo heterozygous variant (c.802 G>A; p.Asp268Asn) in exon 8 of the fetal PRKACB gene (NM_182948.4). According to the ACMG variant-classification guidelines, this variant was interpreted as likely pathogenic (PS2_Moderate, PM1, PM2_Supporting and PP3). AlphaFold-based structural prediction indicated that the PRKACB p.Asp268Asn substitution resulted in the loss of two hydrogen bonds, thereby altering the protein's three-dimensional conformation and affecting structural stability.

Conclusion The PRKACB gene c.802 G>A (p.Asp268Asn) variant is a potential genetic cause of bilateral postaxial polydactyly in the fetus. Identification of this variant expands the known mutational spectrum of PRKACB gene and provides an important reference for genetic counselling and prenatal diagnosis.

Keywords

PRKACB / Postaxial polydactyly / Intrauterine Growth Restriction / Prenatal diagnosis

Consent

Written informed consent was obtained from the parents of the fetus.

Ethical approval

This study was reviewed and approved by the Medical Ethics Committee of Zhejiang Provincial People's Hospital (Approval Number: QT2025076).

Funding

This research was funded by the "Sharp soldier Leading Goose + X" Research and Development Program of Zhejiang Province (2024C03004) and Natural Science Foundation of Zhejiang Province (LY22H160039).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We are grateful to the family who participated in this study.

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