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Updated: Nov 4, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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.
Aims:
Maturity-onset diabetes of the young (MODY) is one of the rare monogenic forms of diabetes. To date, about 12 genes in the scientific literature are closely related to the occurrence of the disease phenotype. However, there is still a high prevalence of undiagnosed cases of so-called MODY-X whose genetic background is still unknown.
Methods:
We performed tNGS for 523 patients with suspected MODY. Next 357 selected patients, in whom no damaging variants were found in 12 major genes causing MODY, were screened for the presence of pathogenic variants in four candidate genes (MNX1, RFX6, NKX2.2, and NKX6.1). All data were generated in one tNGS sequencing reaction and confirmed by Sanger sequencing.
Results:
In total, we selected five potentially damaging variants, in eight patients, in RFX6, NKX2.2, and NKX6.1 genes. Four of them have never been described in literature before. The frequency of occurrence of two of them in the RFX6 gene significantly differed in relation to the healthy population. The analysis of segregation in the family did not reveal that they were the only cause of the disease phenotype.
Conclusions:
The very-rare variants indicated in this study show that this type of research on large population groups may help in the future for better understanding and more accurate diagnostics of extremely rare forms of MODY.
