Abstract
Purpose
Werner syndrome (WS) is a rare autosomal recessive genetic disease caused by mutations in the WRN gene, and it is characterized by multiple manifestations corresponding to early-onset aging. This study reports the case of a WS patient with a novel WRN mutation.
Patient and methods
A 36-year-old male patient with WS was evaluated after approval from the local ethics committee. The clinical and biochemical findings of the patient were described. Peripheral blood sample was collected to extract genomic DNA for WRN gene exome sequencing. The three-dimensional (3D) protein structural prediction analysis was performed via the AlphaFold 2.2 program and PyMol software.
Results
We report the case of a clinically diagnosed WS patient with consanguineous parents who presented with complex manifestations including early-onset diabetes mellitus, binocular cataracts, cerebral infarction, cerebral atherosclerosis, hypertension, dyslipidemia, hypothyroidism, and suspected meningioma, accompanied by short stature, gray hair, rough skin with subcutaneous fat atrophy, a high-pitched voice, palmoplantar keratoderma, bilateral flat feet, and an indolent deep ulceration on the foot. Exome sequencing identified a novel homozygous frameshift mutation in the WRN gene, c.666-669 del TATT, p.I223fs. The 3D structure prediction showed that premature termination and significant structural changes could occur in the mutant WRN protein.
Conclusion
We identified a novel homozygous frameshift mutation, p.I223fs, in WRN in a Chinese patient with WS, expanding the spectrum of mutations in WS.
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Acknowledgements
The authors would like to thank the patient for his contribution and cooperation with the study. We also thank Clinical Medical Experimental Research Center of Fujian Provincial Hospital for providing support of DNA sequencing. The computations in the study were performed on the π2.0 cluster supported by the Center for High Performance Computing of Shanghai Jiao Tong University.
Author contributions
J.Wu, S.P., R.L. and G.C. contributed to the design of the study. S.P., J.Wu, W.L. and J.Wen collected the clinical data. R.L. performed the sequence analysis. J.Wu and S.P. wrote the draft of the manuscript. R.L. and G.C. jointly supervised the work. All the authors have read and approved the final manuscript.
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The authors declare no competing interests.
Ethics approval
The study was approved by the Ethics Committee of Fujian Provincial Hospital, Fuzhou, China (No. K2016-10-032).
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Written informed consent was obtained from the patient included in the study for genome sequencing and publication.
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Wu, J., Pan, S., Lin, W. et al. The identification of a novel mutation (p.I223fs) in WRN associated with Werner syndrome. Endocrine 84, 92–96 (2024). https://doi.org/10.1007/s12020-023-03565-7
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DOI: https://doi.org/10.1007/s12020-023-03565-7