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Screening for extremely rare pathogenic variants of monogenic diabetes using targeted panel sequencing
Tomasz Płoszaj1, Karolina Antosik2, Paulina Jakiel2
1Department of Clinical Genetics, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland. tomasz.ploszaj@umed.lodz.pl.
Endocrine
|May 21, 2021
Summary
This study investigated rare genetic variants in Maturity-onset diabetes of the young (MODY), identifying novel mutations in genes like RFX6. Further research on large populations is crucial for diagnosing rare MODY forms.
Area of Science:
- Genetics
- Endocrinology
- Diabetes Research
Background:
- Maturity-onset diabetes of the young (MODY) is a rare monogenic diabetes.
- Approximately 12 genes are linked to MODY, yet many cases (MODY-X) remain undiagnosed due to unknown genetic causes.
Purpose of the Study:
- To identify novel genetic variants in patients with suspected MODY.
- To investigate the genetic background of undiagnosed MODY-X cases.
Main Methods:
- Targeted next-generation sequencing (tNGS) was performed on 523 suspected MODY patients.
- 357 patients negative for mutations in 12 major MODY genes were screened for variants in MNX1, RFX6, NKX2.2, and NKX6.1.
- Sanger sequencing confirmed identified variants.
Main Results:
- Five potentially damaging variants were identified in eight patients within the RFX6, NKX2.2, and NKX6.1 genes.
- Four of these variants are novel and have not been previously described.
- Two variants in the RFX6 gene showed a significant difference in frequency compared to the healthy population, though segregation analysis did not confirm them as the sole cause of the phenotype.
Conclusions:
- The identified rare variants highlight the potential for discovering new genetic factors in MODY.
- Large-scale population studies are essential for advancing the understanding and diagnosis of extremely rare forms of MODY.
