P109Homozygous hypomorphic HNF1A alleles are a novel cause of Maturity Onset Diabetes of the Young (MODY)S MISRA1,2, N Hassanali3, A Bennett3, A Juszczak3, R Caswell4, J Valabhji2, S Ellard4, NS Oliver1, A Gloyn3,5,61Diabetes, Endocrinology & Metabolism, Imperial College London, London, UK, 2Diabetes & Endocrinology, Imperial College Healthcare NHS Trust, London, UK, 3Oxford Centre for Diabetes Endocrinology & Metabolism, University of Oxford, Oxford, UK, 4Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK, 5Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK, 6Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UKAim: Heterozygous loss‐of‐function (LOF) mutations in hepatocyte nuclear factor 1‐alpha (HNF1A) cause sulphonylurea‐sensitive MODY. In humans, HNF1A homozygous LOF alleles are presumed embryonically lethal. We report the first kindred with a homozygous HNF1A mutation causing sulphonylurea‐sensitive diabetes.Methods: The 27‐year‐old proband was diagnosed aged 15 years with Type 1 diabetes and insulin treated. GAD65 and IA‐2 antibodies were negative and c‐peptide was 622pmol/l, 12‐year post‐diagnosis. The proband's twin developed insulin‐treated diabetes aged 12 years. The mother developed gestational diabetes (29 years), which persisted postpartum. The father aged 63 years is normoglycaemic. We used in vitro and in vivo studies to assess the cause of diabetes.Results: HNF1A sequencing identified a
Diabetic Medicine – Wiley
Published: Jan 1, 2018
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