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Endocrine
Published in: Endocrine 1/2024

19-09-2023 | Maturity-Onset Diabetes of the Young | Original Article

Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes

Authors: Siyu Sun, Siqian Gong, Meng Li, Xirui Wang, Fang Wang, Xiaoling Cai, Wei Liu, Yingying Luo, Simin Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Yumin Ma, Qian Ren, Xiuying Zhang, Jing Chen, Ling Chen, Jing Wu, Leili Gao, Xianghai Zhou, Yufeng Li, Liyong Zhong, Xueyao Han, Linong Ji

Published in: Endocrine | Issue 1/2024

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Abstract

Objective

CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD).

Methods

We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China.

Results

In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted.

Conclusion

CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
Appendix
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Metadata
Title
Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes
Authors
Siyu Sun
Siqian Gong
Meng Li
Xirui Wang
Fang Wang
Xiaoling Cai
Wei Liu
Yingying Luo
Simin Zhang
Rui Zhang
Lingli Zhou
Yu Zhu
Yumin Ma
Qian Ren
Xiuying Zhang
Jing Chen
Ling Chen
Jing Wu
Leili Gao
Xianghai Zhou
Yufeng Li
Liyong Zhong
Xueyao Han
Linong Ji
Publication date
19-09-2023
Publisher
Springer US
Published in
Endocrine / Issue 1/2024
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-023-03512-6

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