Hoff, FW and Xing, C and Simha, V and Agarwal, AK and Zhang, X and Lekkala, L and Vaishnav, MS and Vuitch, F and Garg, A (2023) Early-onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family. In: Molecular Genetics and Genomic Medicine .
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Abstract
Background: Diabetes mellitus (DM) in children and adolescents is typically caused by type 1 DM, followed by type 2 DM and maturity-onset diabetes of the young (MODY). We report an unusual Asian Indian family in which three members presented with DM at ages 15, 20, and 30, but not fitting the typical clinical picture of type 1 DM, type 2 DM, or MODY. The primary objective was to elucidate the molecular genetic basis of DM in this family. Methods: The proband, a 22-year-old man, had short stature, gray hair, osteoporosis, and markedly reduced subcutaneous fat on the body, especially on the extremities along with acanthosis nigricans, and developed myxoid malignant peripheral nerve sheath tumor. Detailed family history revealed multiple loops of consanguinity. The proband underwent whole-genome sequencing, and seven relatives underwent whole-exome sequencing. Results: The proband and three additional family members were found to have the homozygous c.561A>G nucleotide variant of WRN RecQ-like helicase (WRN) gene consistent with the diagnosis of Werner's syndrome. The c.561A>G variant induces a new splicing site on exon 6 resulting in a truncated WRN protein, p.Lys187Trpfs*13. Conclusion: Our report brings to attention the onset of DM during childhood or early adulthood in patients with Werner's syndrome who typically develop type 2 DM around the age of 30–40 years. Presence of consanguinity among parents, dysmorphic features, and malignancy should prompt consideration of diagnosis of Werner's syndrome. © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
| Item Type: | Journal Article |
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| Publication: | Molecular Genetics and Genomic Medicine |
| Publisher: | John Wiley and Sons Inc |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | diabetes mellitus, lipodystrophy, myxoid malignant peripheral nerve sheath tumor, Werner's syndrome, WRN |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Nano Science and Engineering |
| Date Deposited: | 18 Dec 2023 04:06 |
| Last Modified: | 18 Dec 2023 04:06 |
| URI: | https://eprints.iisc.ac.in/id/eprint/83499 |
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