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

• Published in: Endocrine 2024-01, Vol.83 (1), p.99-109
• Main Authors: Sun, Siyu, Gong, Siqian, Li, Meng, Wang, Xirui, Wang, Fang, Cai, Xiaoling, Liu, Wei, Luo, Yingying, Zhang, Simin, Zhang, Rui, Zhou, Lingli, Zhu, Yu, Ma, Yumin, Ren, Qian, Zhang, Xiuying, Chen, Jing, Chen, Ling, Wu, Jing, Gao, Leili, Zhou, Xianghai, Li, Yufeng, Zhong, Liyong, Han, Xueyao, Ji, Linong
• Format: Article
• Language: English
• Subjects: Age; Atrophy; Carboxylesterase - genetics; CEL gene; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Elastase; Endocrinology; Frameshift mutation; Genetic screening; Humanities and Social Sciences; Humans; Internal Medicine; Lipomatosis; Literature reviews; Medicine; Medicine & Public Health; Missense mutation; multidisciplinary; Mutation; Original Article; Pancreas; Pancreas, Exocrine; Pancreatitis; Science
• ISSN: 1559-0100; 1355-008X; 1559-0100
• DOI: 10.1007/s12020-023-03512-6

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.