biostudies-literatureUnknown15(2)Takase K<h4>Aims</h4>We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center.<h4>Methods</h4>We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history.<h4>Results</h4>Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the <i>GCK</i> and <i>WFS1</i> genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the <i>HNF4A</i> gene. Twelve variants remained as candidates associated with the development of diabetes.<h4>Conclusion</h4>Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1007/s13340-023-00669-3.Diabetology international203-211https://www.ebi.ac.uk/biostudies/studies/S-EPMC10959868biostudies-literatureIdentification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study.PMC10959868Karasawa SNagaoka KKameda WTakase KIshizawa KNumakura CSusa SHada YSato HTakakubo NfalseIdentification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study.<h4>Aims</h4>We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center.<h4>Methods</h4>We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history.<h4>Results</h4>Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the <i>GCK</i> and <i>WFS1</i> genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the <i>HNF4A</i> gene. Twelve variants remained as candidates associated with the development of diabetes.<h4>Conclusion</h4>Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1007/s13340-023-00669-3.2024-01-01T00:00:00Z2024 Apr2026-06-01T17:41:45.908Z2025-04-06T18:27:40.366ZS-EPMC109598683852493210.1007/s13340-023-00669-3