{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(2)"],"submitter":["Takase K"],"pubmed_abstract":["<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."],"journal":["Diabetology international"],"pagination":["203-211"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10959868"],"repository":["biostudies-literature"],"pubmed_title":["Identification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study."],"pmcid":["PMC10959868"],"pubmed_authors":["Karasawa S","Nagaoka K","Kameda W","Takase K","Ishizawa K","Numakura C","Susa S","Hada Y","Sato H","Takakubo N"],"additional_accession":[]},"is_claimable":false,"name":"Identification of causative gene variants for patients with known monogenic diabetes using a targeted next-generation sequencing panel in a single-center study.","description":"<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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T17:41:45.908Z","creation":"2025-04-06T18:27:40.366Z"},"accession":"S-EPMC10959868","cross_references":{"pubmed":["38524932"],"doi":["10.1007/s13340-023-00669-3"]}}