{"id":180,"date":"2022-07-25T12:57:16","date_gmt":"2022-07-25T12:57:16","guid":{"rendered":"https:\/\/web.ucdr.be\/wordpress\/\/?page_id=180"},"modified":"2024-05-08T10:57:30","modified_gmt":"2024-05-08T08:57:30","slug":"publications","status":"publish","type":"page","link":"https:\/\/www.ucdr.be\/index.php\/publications\/","title":{"rendered":"Publications"},"content":{"rendered":"\t\t
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115 entries<\/span> «<\/a> ‹<\/a> 1 of 3 ›<\/a> »<\/a> <\/div><\/div>

2026<\/h3>

Yue Tong; Marianne Becker; Ulrike Schierloh; Fl\u00e1via Natividade da Silva; Leena Haataja; Ying Cai; Kashyap A Patel; Farah Kobaisi; Uyenlinh L Mirshahi; Kevin Colclough; Muhammad Shabab Javed; Matthew N Wakeling; Federica Fantuzzi; Maria Lytrivi; Toshiaki Sawatani; Maria Nicol Arroyo; Xiaoyan Yi; Chiara Vinci; Hossam Montaser; Nathalie Pachera; Timo Otonkoski; Mariana Igoillo-Esteve; Rapha\u00ebl Scharfmann; Andrew T Hattersley; Peter Arvan; Carine De Beaufort; Miriam Cnop<\/p>

A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data<\/a> Journal Article<\/span> <\/p>

In: <\/span>EMBO Mol Med, <\/span>vol. 18, <\/span>no. 2, <\/span>pp. 620\u2013645, <\/span>2026<\/span>, ISSN: 1757-4684<\/span>.<\/p>

Abstract<\/a><\/span> | Links<\/a><\/span><\/p>

@article{pmid41484206,
\r\ntitle = {A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data},
\r\nauthor = {Yue Tong and Marianne Becker and Ulrike Schierloh and Fl\u00e1via Natividade da Silva and Leena Haataja and Ying Cai and Kashyap A Patel and Farah Kobaisi and Uyenlinh L Mirshahi and Kevin Colclough and Muhammad Shabab Javed and Matthew N Wakeling and Federica Fantuzzi and Maria Lytrivi and Toshiaki Sawatani and Maria Nicol Arroyo and Xiaoyan Yi and Chiara Vinci and Hossam Montaser and Nathalie Pachera and Timo Otonkoski and Mariana Igoillo-Esteve and Rapha\u00ebl Scharfmann and Andrew T Hattersley and Peter Arvan and Carine De Beaufort and Miriam Cnop},
\r\ndoi = {10.1038\/s44321-025-00362-9},
\r\nissn = {1757-4684},
\r\nyear  = {2026},
\r\ndate = {2026-02-01},
\r\njournal = {EMBO Mol Med},
\r\nvolume = {18},
\r\nnumber = {2},
\r\npages = {620--645},
\r\nabstract = {The INS c.16\u2009C\u2009>\u2009T (insulin p.Arg6Cys, R6C) variant was reported to cause autosomal dominant monogenic diabetes, yet its pathogenicity has been questioned. R6C preproinsulin exhibits impaired translocation into the endoplasmic reticulum (ER). We explored R6C pathogenicity using integrative clinical, genetic, and functional approaches.Homozygous INS R6C individuals presented early-onset insulin-treated diabetes, whereas heterozygous carriers showed variable or absent glycemic phenotypes. Population-level analysis revealed no significant enrichment of diabetes among heterozygotes. Heterozygous R6C patient's induced pluripotent stem cell (iPSC)-derived pancreatic \u03b2 cells exhibited minimal defects, while homozygous R6C \u03b2 cells displayed preproinsulin accumulation and reduced insulin content and secretion. In vivo, homozygous R6C \u03b2 cell transplants recapitulated insulin deficiency and responded poorly to GLP-1 receptor agonist. Homozygous R6C \u03b2 cells had a gene signature of attenuated translation, translocation and ER related pathways.Our findings establish R6C as a recessive loss-of-function mutation, prompting a clinical reassessment of heterozygous R6C carriers. This study highlights the power of population genetic databases, patients' iPSC-based modeling and multi-modal variant classification frameworks for dissecting the consequences of genetic variants in monogenic diabetes.},
\r\nkeywords = {},
\r\npubstate = {published},
\r\ntppubtype = {article}
\r\n}
\r\n<\/pre><\/div>
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The INS c.16\u2009C\u2009>\u2009T (insulin p.Arg6Cys, R6C) variant was reported to cause autosomal dominant monogenic diabetes, yet its pathogenicity has been questioned. R6C preproinsulin exhibits impaired translocation into the endoplasmic reticulum (ER). We explored R6C pathogenicity using integrative clinical, genetic, and functional approaches.Homozygous INS R6C individuals presented early-onset insulin-treated diabetes, whereas heterozygous carriers showed variable or absent glycemic phenotypes. Population-level analysis revealed no significant enrichment of diabetes among heterozygotes. Heterozygous R6C patient’s induced pluripotent stem cell (iPSC)-derived pancreatic \u03b2 cells exhibited minimal defects, while homozygous R6C \u03b2 cells displayed preproinsulin accumulation and reduced insulin content and secretion. In vivo, homozygous R6C \u03b2 cell transplants recapitulated insulin deficiency and responded poorly to GLP-1 receptor agonist. Homozygous R6C \u03b2 cells had a gene signature of attenuated translation, translocation and ER related pathways.Our findings establish R6C as a recessive loss-of-function mutation, prompting a clinical reassessment of heterozygous R6C carriers. This study highlights the power of population genetic databases, patients’ iPSC-based modeling and multi-modal variant classification frameworks for dissecting the consequences of genetic variants in monogenic diabetes.<\/div>
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