{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:10:30Z","timestamp":1696309830216},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Maturity\u2010onset diabetes of the young (<jats:styled-content style=\"fixed-case\">MODY<\/jats:styled-content>) caused by heterozygous mutations in the glucokinase (<jats:italic><jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content><\/jats:italic>) gene typically presents with lifelong, stable, mild fasting hyperglycaemia. With the exception of pregnancy, patients with <jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MODY<\/jats:styled-content> usually do not require pharmacological therapy. We report two unrelated patients whose initial genetic test results indicated a deletion of <jats:italic><jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content><\/jats:italic> exon\u00a010, but whose clinical phenotypes were not typical of <jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MODY<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case reports<\/jats:title><jats:p>In case\u00a01, the patient was hyperglycaemic at diagnosis (glucose &gt;\u00a030\u00a0mmol\/l) and elevated glucose levels &gt;\u00a010\u00a0mmol\/l persisted after withdrawal of insulin therapy. The patient in case\u00a02 was also hyperglycaemic at diagnosis [HbA<jats:sub>1c<\/jats:sub> &gt;\u00a086\u00a0mmol\/mol (10%)], which improved with the introduction of oral hypoglycaemic agents. These clinical features were not consistent with <jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MODY<\/jats:styled-content>. Both patients had a single nucleotide variant that prevented multiplex ligation\u2010dependent probe analysis, which generated a false positive result of a <jats:italic><jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content><\/jats:italic> exon\u00a010 deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>False positive genetic results in these two unrelated cases were attributable to the presence of a rare single nucleotide variant that prevented ligation of the probe in the multiplex ligation\u2010dependent probe analysis kit used and falsely indicated deletion of exon\u00a010 within <jats:italic><jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content><\/jats:italic>. Both cases had clinical features that did not tally with the typical <jats:styled-content style=\"fixed-case\">GCK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MODY<\/jats:styled-content> phenotype. These cases emphasize the need to interpret the results of definitive genetic tests within the specific clinical context. Increased medical sequencing is likely to lead to more reports of novel mutations of uncertain significance. If genetic investigations do not agree with the clinical picture, clinicians should exercise caution when making therapeutic changes based on these results.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12210","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T08:47:10Z","timestamp":1366102030000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Atypical phenotype associated with reported <i><scp>GCK<\/scp><\/i> exon\u00a010 deletions: clinical judgement is needed alongside appropriate genetic investigations"],"prefix":"10.1111","volume":"30","author":[{"given":"G.","family":"Thanabalasingham","sequence":"first","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM) University of Oxford Oxford UK"},{"name":"Oxford NIHR Biomedical Research Centre Churchill Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Kaur","sequence":"additional","affiliation":[{"name":"Oxford NIHR Biomedical Research Centre Churchill Hospital Oxford UK"},{"name":"Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Talbot","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology Hinchingbrooke Health Care NHS Trust Huntingdon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Colclough","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Royal Devon and Exeter NHS Foundation Trust Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology Hinchingbrooke Health Care NHS Trust Huntingdon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Oxford NIHR Biomedical Research Centre Churchill Hospital Oxford UK"},{"name":"Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Ellard","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Royal Devon and Exeter NHS Foundation Trust Exeter UK"},{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. R.","family":"Owen","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM) University of Oxford Oxford UK"},{"name":"Oxford NIHR Biomedical Research Centre Churchill Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,7,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400611"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1799-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6044"},{"key":"e_1_2_6_5_1","first-page":"6","article-title":"Finding a glucokinase mutation alters patient's treatment","volume":"24","author":"Gill\u2010Carey O","year":"2007","journal-title":"Diabet Med"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0798-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03214.x"},{"key":"e_1_2_6_8_1","first-page":"768610","article-title":"A de novo whole GCK gene deletion not detected by gene sequencing, in a boy with phenotypic GCK insufficiency","volume":"2011","author":"Birkebaek NH","year":"2011","journal-title":"Case Rep Genet"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21110"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-0942-y"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnf056"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4149\/endo_2012_02_99"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-011-0300-2"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.080004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0204-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.4.921"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1677"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1243"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037423"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038050"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2194-5"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-2420"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12210","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:46:08Z","timestamp":1696221968000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,16]]},"references-count":21,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/dme.12210"],"URL":"https:\/\/doi.org\/10.1111\/dme.12210","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,16]]},"assertion":[{"value":"2013-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}