{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:44:28Z","timestamp":1793400268418,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.bioscientifica.com\/journals\/reuselicenceeje\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (<jats:italic>ABCC8<\/jats:italic>,<jats:italic>KCNJ11<\/jats:italic>,<jats:italic>GLUD1<\/jats:italic>,<jats:italic>GCK<\/jats:italic>,<jats:italic>HADH<\/jats:italic>,<jats:italic>SLC16A1<\/jats:italic>,<jats:italic>HNF4A<\/jats:italic>and<jats:italic>HNF1A<\/jats:italic>) are known to cause CHI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterise the clinical and molecular aspects of a large cohort of patients with CHI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Three hundred patients were recruited and clinical information was collected before genotyping.<jats:italic>ABCC8<\/jats:italic>and<jats:italic>KCNJ11<\/jats:italic>genes were analysed in all patients. Mutations in<jats:italic>GLUD1<\/jats:italic>,<jats:italic>HADH<\/jats:italic>,<jats:italic>GCK<\/jats:italic>and<jats:italic>HNF4A<\/jats:italic>genes were sought in patients with diazoxide-responsive CHI with hyperammonaemia (<jats:italic>GLUD1<\/jats:italic>), raised 3-hydroxybutyrylcarnitine and\/or consanguinity (<jats:italic>HADH<\/jats:italic>), positive family history (<jats:italic>GCK<\/jats:italic>) or when CHI was diagnosed within the first week of life (<jats:italic>HNF4A<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutations were identified in 136\/300 patients (45.3%). Mutations in<jats:italic>ABCC8\/KCNJ11<\/jats:italic>were the commonest genetic cause identified (<jats:italic>n<\/jats:italic>=109, 36.3%). Among diazoxide-unresponsive patients (<jats:italic>n<\/jats:italic>=105), mutations in<jats:italic>ABCC8\/KCNJ11<\/jats:italic>were identified in 92 (87.6%) patients, of whom 63 patients had recessively inherited mutations while four patients had dominantly inherited mutations. A paternal mutation in the<jats:italic>ABCC8\/KCNJ11<\/jats:italic>genes was identified in 23 diazoxide-unresponsive patients, of whom six had diffuse disease. Among the diazoxide-responsive patients (<jats:italic>n<\/jats:italic>=183), mutations were identified in 41 patients (22.4%). These include mutations in<jats:italic>ABCC8\/KCNJ11<\/jats:italic>(<jats:italic>n<\/jats:italic>=15),<jats:italic>HNF4A<\/jats:italic>(<jats:italic>n<\/jats:italic>=7),<jats:italic>GLUD1<\/jats:italic>(<jats:italic>n<\/jats:italic>=16) and<jats:italic>HADH<\/jats:italic>(<jats:italic>n<\/jats:italic>=3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A genetic diagnosis was made for 45.3% of patients in this large series. Mutations in the<jats:italic>ABCC8<\/jats:italic>gene were the commonest identifiable cause. The vast majority of patients with diazoxide-responsive CHI (77.6%) had no identifiable mutations, suggesting other genetic and\/or environmental mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-12-0673","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T10:26:29Z","timestamp":1359023189000},"page":"557-564","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":210,"title":["Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism"],"prefix":"10.1093","volume":"168","author":[{"given":"Ritika R","family":"Kapoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ved Bhushan","family":"Arya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian P","family":"Shield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"1","key":"1_16885125","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s004310100847","volume":"161","author":"de Lonlay","year":"2002","journal-title":"European journal of pediatrics","ISSN":"https:\/\/id.crossref.org\/issn\/0340-6199","issn-type":"print"},{"issue":"2","key":"4_6480324","doi-asserted-by":"publisher","first-page":"F98","DOI":"10.1136\/fn.82.2.F98","volume":"82","author":"Aynsley-Green","year":"2000","journal-title":"Archives of Disease in Childhood - Fetal and Neonatal Edition","ISSN":"https:\/\/id.crossref.org\/issn\/1359-2998","issn-type":"print"},{"issue":"3","key":"5_11062824","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1067\/mpd.2001.111818","volume":"138","author":"Hsu","year":"2001","journal-title":"The Journal of pediatrics","ISSN":"https:\/\/id.crossref.org\/issn\/0022-3476","issn-type":"print"},{"key":"6_45420286","doi-asserted-by":"crossref","first-page":"118e","DOI":"10.1371\/journal.pmed.0040118","volume":"4","year":"2007","journal-title":"PLOS MEDICINE"},{"issue":"5","key":"7_34177011","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1136\/jmg.2008.064337","volume":"46","year":"2009","journal-title":"Journal of Medical Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0022-2593","issn-type":"print"},{"issue":"10","key":"8_43197893","doi-asserted-by":"publisher","first-page":"E2026","DOI":"10.1210\/jc.2012-1356","volume":"97","year":"2012","journal-title":"Journal of Clinical Endocrinology &amp; 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