A novel homozygous missense DNAJC3 variant in syndromic juvenile-onset diabetes

Eda Mengen; Deniz Kor; Fatma Derya Bulut; Leman Damla Kotan; İhsan Turan; Bilgin Yüksel; Neslihan Önenli Mungan

doi:10.1515/jpem-2025-0072

Artikel

A novel homozygous missense DNAJC3 variant in syndromic juvenile-onset diabetes

Eda Mengen , Deniz Kor , Fatma Derya Bulut , Leman Damla Kotan , İhsan Turan , Bilgin Yüksel und Neslihan Önenli Mungan

Veröffentlicht/Copyright: 20. Juni 2025

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Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 38 Heft 9

Abstract

Objectives

The DNAJC3 gene encodes a protein that acts as a cochaperone of binding immunoglobulin protein (BiP), a major member of the heat shock protein 70 (HSP70) family, which is found in the endoplasmic reticulum (ER) and promotes normal protein folding. Loss-of-function mutations in DNAJC3 lead to early-onset diabetes and multisystemic neurodegeneration. In this article, we report a case of monogenic syndromic diabetes caused by a previously undescribed DNAJC3 variant.

Case presentation

A 15-year-old 5-month-old girl with polyuria and polydipsia for the last 2–3 months was diagnosed and treated as diabetic ketoacidosis at the center where she was admitted with complaints of general condition disorder and frequent breathing. Her laboratory findings were HbA_1c 15.1 %, serum insulin 7.83 m U/L, C-peptide 0.78 μg/L. Tests for autoimmune diabetes markers were negative. Physical examination revealed severe short stature 141.4 cm (−3.62 SDS). Sensorineural hearing loss developed 5 months after the diagnosis of diabetes and intellectual functions were impaired. Neurologic examination revealed marked ataxia. Monogenic syndromic diabetes mellitus with multisystemic neurodegeneration including juvenile onset diabetes mellitus, ataxia, short stature and sensorineural hearing loss was considered. Exome sequencing and CNV (Copy Number Variation) analysis revealed a novel homozygous c.1244G>C (p.Arg415Pro) variant in DNAJC3 gene.

Conclusions

This case supports the wide phenotypic spectrum and multisystem involvement potential of DNAJC3 variants and demonstrates the need to increase awareness in the diagnostic process of these rare genetic disorders..

Keywords: monogenic diabetes; DNAJC3 ; neurodegeneration; endoplasmic reticulum

Corresponding author: Eda Mengen, Department of Pediatric Endocrinology, Faculty of Medicine, Çukurova University, 01330, Adana, Türkiye, E-mail: emengen@cu.edu.tr

Acknowledgments

We acknowledge the contributions of the clinical laboratory and radiology departments for their assistance in the diagnostic evaluation of the patient.

Research ethics: As this is a case report, formal approval from an Ethics Committee was not required.
Informed consent: Informed consent for publication of case details was obtained from the patient’s parents.
Author contributions: Eda Mengen, Deniz Kor, İhsan Turan, Neslihan Önenli Mungan and Fatma Derya Bulut collected the patient data. Eda Mengen wrote the manuscript. Eda Mengen and Damla Kotan worked on the family pedigree. Damla Kotan revised the genetic aspects of the study. Neslihan Mungan and Bilgin Yüksel revised the manuscript. Neslihan Mungan supervised the entire process, as well as revised and approved the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2025-02-12

Accepted: 2025-06-09

Published Online: 2025-06-20

Published in Print: 2025-09-25

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Artikel in diesem Heft

https://doi.org/10.1515/jpem-2025-0072

Schlagwörter für diesen Artikel

monogenic diabetes; DNAJC3; neurodegeneration; endoplasmic reticulum