{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:49Z","timestamp":1789621489730,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008235","name":"Peking Union Medical College Hospital","doi-asserted-by":"publisher","award":["2022-PUMCH-A-134, 2022-PUMCH-A-048"],"award-info":[{"award-number":["2022-PUMCH-A-134, 2022-PUMCH-A-048"]}],"id":[{"id":"10.13039\/501100008235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Maturity-onset diabetes of the young (MODY) comprises a heterogeneous group of autosomal dominant monogenic diabetes disorders; accurate molecular diagnosis is essential, as different subtypes require fundamentally distinct management strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In a Chinese pedigree initially misdiagnosed as MODY10 based on an incidental INS variant, we aimed to identify the true genetic etiology through comprehensive genetic analysis (including copy number variation [CNV] detection) and continuous glucose monitoring (CGM), and to illustrate the clinical consequences of rigorous variant interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Detailed clinical evaluation, whole-exome sequencing (WES), whole-genome sequencing (WGS), multiplex ligation-dependent probe amplification (MLPA), segregation analysis, and CGM monitoring were performed across three generations of the pedigree.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a 1, 171 bp GCK deletion (chr7:44, 228, 224-44, 229, 394 [GRCh37], encompassing the \u03b2-cell promoter, exon 1, and part of intron 1) that co-segregated with diabetes across three generations. This deletion removes the \u03b2-cell promoter while leaving the hepatic promoter intact, predicting selective loss of the pancreatic glucokinase isoform. The deletion was classified as pathogenic under ACMG\/AMP criteria using the ClinGen Monogenic Diabetes Expert Panel specifications. Segregation analysis revealed that an INS variant (NM_000207.3:c.4G&amp;gt;A, p.Ala2Thr; rs535989053) did not co-segregate with diabetes: it was inherited from the euglycaemic maternal grandfather (fasting glucose 5.0 mmol\/L, HbA1c 5.2%) and was absent in the proband. Under ACMG\/AMP criteria, the INS variant meets criteria for a benign allele (BS1, BP2). The proband (isolated MODY2) exhibited a characteristic \u201cplateau-like\u201d stable mild hyperglycemia (coefficient of variation [CV] 14.35%). The elder brother, who carries both variants, showed a similar stable pattern (CV 13.41%). The mother, who also carries both variants, had been treated with insulin for ten years under the erroneous MODY10 diagnosis; upon discontinuation of insulin, her glycemic control remained stable, with CGM metrics comparable to those of her children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case underscores the critical importance of CNV analysis and segregation studies in monogenic diabetes diagnostics. The identification of a large GCK deletion corrected the initial misdiagnosis of MODY10\u2014based on an incidental INS variant\u2014and enabled appropriate genetic counseling and discontinuation of unnecessary insulin therapy. CGM emerges as a valuable ancillary tool for distinguishing MODY2 from MODY10 and for reassuring patients that pharmacological treatment is not required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1967659","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:46:46Z","timestamp":1789620406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A novel 1, 171 bp GCK promoter\/exon 1 deletion in a Chinese pedigree: correcting a misdiagnosis of MODY10 based on an incidental INS variant"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiahui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics, and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tsinghua University","place":["Beijing, China"]},{"name":"Peking Union Medical College Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianze","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital","place":["Beijing, China"]},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-0942-y","article-title":"Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young","volume":"51","author":"Ellard","year":"2008","journal-title":"Diabetologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13098-021-00716-6","article-title":"Clinical and genetic features of maturity-onset diabetes of the young in pediatric patients: a 12-year monocentric experience","volume":"13","author":"Passanisi","year":"2021","journal-title":"Diabetol Metab Syndrome"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dci20-0065","article-title":"Monogenic diabetes: From genetic insights to population-based precision in care. 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