دورية أكاديمية
High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism.
| العنوان: | High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism. |
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| المؤلفون: | Rozenkova K; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Malikova J; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Nessa A; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Dusatkova L; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Bjørkhaug L; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Obermannova B; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Dusatkova P; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Kytnarova J; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Aukrust I; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Najmi LA; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Rypackova B; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Sumnik Z; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Lebl J; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Njølstad PR; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Hussain K; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom., Pruhova S; Department of Paediatrics, Second Faculty of Medicine (K.R., J.M., L.D., B.O., P.D., Z.S., J.L., S.P.), Charles University in Prague and University Hospital in Motol, Prague 150 06, Czech Republic; Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (A.N., K.H.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom; KG Jebsen Center for Diabetes Research, Department of Clinical Science (L.B., I.A., L.A.N., P.R.N.), University of Bergen, Bergen N-5021, Norway; Department of Biomedicine (L.B.), University of Bergen, Bergen N-5021, Norway; Department of Paediatrics, First Faculty of Medicine (J.K.), Charles University in Prague and the General University Hospital in Prague, Prague 121 08, Czech Republic; Center for Medical Genetics and Molecular Medicine (I.A., L.A.N.), Haukeland University Hospital, Bergen N-5021, Norway; Center for Research of Diabetes, Metabolism and Nutrition and Second Department of Internal Medicine FNKV, Third Faculty of Medicine (B.R.), Charles University in Prague, Prague 100 00, Czech Republic; Department of Pediatrics (P.R.N.), Haukeland University Hospital, Bergen, N-5020 Norway; and Department of Paediatric Endocrinology (K.H.), Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, United Kingdom. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2015 Dec; Vol. 100 (12), pp. E1540-9. Date of Electronic Publication: 2015 Oct 02. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Congenital Hyperinsulinism/*epidemiology , Congenital Hyperinsulinism/*genetics , Hepatocyte Nuclear Factor 1-alpha/*genetics , Sulfonylurea Receptors/*genetics, Adult ; Child, Preschool ; Cohort Studies ; Czech Republic/epidemiology ; DNA/genetics ; Female ; Genetic Variation ; Germinal Center Kinases ; Hepatocyte Nuclear Factor 4/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation/genetics ; Pedigree ; Potassium Channels, Inwardly Rectifying/genetics ; Pregnancy ; Protein Serine-Threonine Kinases/genetics ; Rubidium Radioisotopes ; Transcriptional Activation |
| مستخلص: | Context: Congenital hyperinsulinism of infancy (CHI) represents a group of heterogeneous disorders characterized by oversecretion of insulin from pancreatic β-cells causing severe hypoglycemia. Objective: We studied the distribution of genetic causes of CHI in a Czech population. Methods: Countrywide collection of patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk [interquartile range, 1-612 wk]). We sequenced the ABCC8, KCNJ11, GLUD1, GCK, HADH, UCP2, SLC16A1, HNF4A, and HNF1A genes and investigated structural changes in the ABCC8 gene. We functionally tested novel variants in the ABCC8 gene by Rb(86+) efflux assay and novel variants in the HNF1A gene by transcriptional activation and DNA-binding tests. Results: We found causal mutations in 20 subjects (50%): 19 carried a heterozygous mutation while one patient was homozygous for mutation in the ABCC8 gene. Specifically, we detected 11 mutations (seven novel) in ABCC8, one novel mutation in KCNJ11, five mutations (two novel) in HNF1A, two novel mutations in HNF4A, and one in GCK. We showed a decrease of activation by diazoxide in mutant KATP channels with novel ABCC8 variants by 41-91% (median, 82%) compared with wild-type (WT) channels and reduced transcriptional activity of mutant HNF1A proteins (2.9% for p.Asn62Lysfs93* and 22% for p.Leu254Gln) accompanied by no DNA-binding ability compared with WT HNF1A. Conclusion: We detected a higher proportion of heterozygous mutations causing CHI compared with other cohorts probably due to lack of consanguinity and inclusion of milder CHI forms. Interestingly, HNF1A gene mutations represented the second most frequent genetic cause of CHI in the Czech Republic. Based on our results we present a genetic testing strategy specific for similar populations. |
| المشرفين على المادة: | 0 (ABCC8 protein, human) 0 (Germinal Center Kinases) 0 (HNF1A protein, human) 0 (HNF4A protein, human) 0 (Hepatocyte Nuclear Factor 1-alpha) 0 (Hepatocyte Nuclear Factor 4) 0 (Kir6.2 channel) 0 (Potassium Channels, Inwardly Rectifying) 0 (Rubidium Radioisotopes) 0 (Sulfonylurea Receptors) 9007-49-2 (DNA) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20151003 Date Completed: 20160419 Latest Revision: 20211203 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1210/jc.2015-2763 |
| PMID: | 26431509 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
|---|---|
| DOI: | 10.1210/jc.2015-2763 |