Two new mutations in the CEL gene causing diabetes and hereditary pancreatitis: How to correctly identify MODY8 cases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F22%3A10434681" target="_blank" >RIV/00216208:11130/22:10434681 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/22:10434681
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2Gh5LKf1ns" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2Gh5LKf1ns</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1210/clinem/dgab864" target="_blank" >10.1210/clinem/dgab864</a>
Alternative languages
Result language
angličtina
Original language name
Two new mutations in the CEL gene causing diabetes and hereditary pancreatitis: How to correctly identify MODY8 cases
Original language description
OBJECTIVE: Maturity-onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. To facilitate correct MODY8 diagnostics, we screened two cohorts of diabetes patients and delineated the phenotype. RESEARCH DESIGN: Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. RESULTS: One Swedish and one Czech case with germline mutation in CEL were identified. Clinical and radiological investigations of these two probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in one pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. CONCLUSIONS: The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30202 - Endocrinology and metabolism (including diabetes, hormones)
Result continuities
Project
<a href="/en/project/NV18-01-00078" target="_blank" >NV18-01-00078: Pancreatic beta cell-related genes and their role in the pathogenesis and treatment of monogenic diabetes</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The Journal of Clinical Endocrinology & Metabolism
ISSN
0021-972X
e-ISSN
1945-7197
Volume of the periodical
107
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
"E1455"-"E1466"
UT code for WoS article
000773033100035
EID of the result in the Scopus database
2-s2.0-85127906982