Molecular genetic study in a cohort of Iranian families suspected to maturity-onset diabetes of the young, reveals a recurrent mutation and a high-risk variant in the CEL gene

Sarmadi, Akram; Mohammadi, Aliasgar; Tabatabaei, Fatemeh; Nouri, Zahra; Chaleshtori, Morteza Hashemzadeh; Tabatabaiefar, Mohammad Amin

doi:10.4103/abr.abr_18_20

Cited by 6 publications

(1 citation statement)

References 45 publications

(45 reference statements)

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“…Mentioned Kuwaiti study and other studies in Iran, rstly chose phenotypically possible MODY cases for detecting causal variants. This is while the reported variants may have a high allele frequency when evaluating the whole population genetic spectrum, which makes them unlikely to be causative for a monogenic rare disease [5,[47][48][49]. Also, as some MODY subtypes like GCK-MODY2 mostly show mild hyperglycemia which is sometimes even undetectable, an exclusive clinical approach to select samples based on phenotype for nding causative mutation seems inadequate.…”

Section: Discussionmentioning

confidence: 99%

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

Asgarian,

Lanjanian,

Anaraki

et al. 2024

Preprint

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Maturity-onset diabetes of the young (MODY) is an uncommon monogenic type of diabetes mellitus. Detecting genetic biomarkers for MODY is a necessity for precise diagnosis and treatment. The majority of MODY genetic predisposition has been documented in European populations and a lack of information is present in Iranians which leads to misdiagnosis as a consequence of defects in unknown variants. In this study, using genetic variant information of 20,002 participants from the family-based TCGS (Tehran cardiometabolic genetic study) cohort, we evaluated the genetic spectrum of MODY in Iran. We concentrated on 14 previously discovered and two novel MODY-causing genes (RFX6 and NKX6-1) that were thought to be responsible for MODY. To find disease-causing mutations, genetic variants were evaluated for their pathogenicity. We discovered 6 mutations that were previously reported in the ClinVar as pathogenic/likely pathogenic (P/LP) for MODY in 45 participants from 24 families. Three potentially novel MODY-causing mutations were also identified, which showed complete disease penetrance (100%) in 10 subjects from 5 families. This is the first family-based study to define the genetic spectrum and estimate the prevalence of MODY in the Iran. The newly discovered mutations need to be investigated by additional studies.

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Section: Discussionmentioning

confidence: 99%

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

Asgarian,

Lanjanian,

Anaraki

et al. 2024

Preprint

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Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients

Yilmaz-Aydogan

Gül

Demirci

et al. 2022

OMICS: A Journal of Integrative Biology

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Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

Jellas

Dušátková

Haldorsen

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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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.

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Molecular genetic study in a cohort of Iranian families suspected to maturity-onset diabetes of the young, reveals a recurrent mutation and a high-risk variant in the CEL gene

Cited by 6 publications

References 45 publications

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

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