Test name: Neonatal Diabetes 22 Gene Panel UKGTN Testing Criteria Approved name and symbol of disorder/condition(s): See Appendix 1 Approved name and symbol of gene(s): See Appendix 1 number(s): number(s): Patient name: Patient postcode: Date of birth: NHS number: Name of referrer: Title/Position: Lab ID: Referrals will only be accept one of the following: Referrer Consultant Endocrinologists Consultant Paediatricians Consultant Clinical Geneticists Tick if this refers to you. Minimum criteria required for testing to be appropriate as stated in the Gene Dossier: Criteria Tick if this patient meets criteria Diabetes diagnosed before 6 months Additional Information: For panel tests: At risk family members where familial mutation is known do not require a full panel test but should be offered analysis of the known mutation If the sample does not fulfil the clinical criteria or you are not one of the specified types of referrer and you still feel that testing should be performed please contact the laboratory to discuss testing of the sample. A
Appendix 1 Genes in panel test and associated conditions. Highlighted rows indicate genes that were being fully analysed in the context of a single separate UKGTN test when the gene dossier was submitted for evaluation. HGNC standard HGNC standard Mode Evidence of % of horizontal MLPA Comments name and number Number name of condition of Number association between coverage of symbol of the and symbol inherit gene(s) and condition gene gene ance Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) ATP- binding cassette, subfamily C (CFTR/MRP), member 8 (ABCC8) ATP- binding cassette, subfamily C (CFTR/MRP), member 8 (ABCC8) 6257 600937 Permanent mellitus 6257 600937 Transient Neonatal diabetes mellitus 59 600509 Permanent mellitus. familial 1, 256450 59 600509 Transient neonatal diabetes mellitus familial 1, 256450 Insulin (INS) 6081 176730 Permanent Neonatal diabetes mellitus and and reces 606176 Gloyn et al 2004 N Engl J Med 350, 1838-1849 610582 Gloyn et al 2005 HMG 14: 925-34; Edghill et al 2007 J Clin Endocrinol Metab 92:1773-7 606176 Babenko et al 2006, NEJM 355:456-466 Flanagan et al 2007 Diabetes 56, 1930-1937, 606176 Stoy et al PNAS 104, 15040-15044, Edghill et al 2008 Diabetes 57,1034-1042, Garin et al 2010 PNAS 107, 3105-3110 100% of minimal promoter region, coding region and
Forkhead box P3 (FOXP3) Eukaryotic translation initiation factor 2- alpha kinase 3 (EIF2AK3) GATA binding protein 6 (GATA6) GATA binding protein 4 (GATA4) Glucokinase (GCK) GLIS family zinc finger 3 (GLIS3) 6106 300292 IPEX syndrome X- linked reces 3255 604032 Wolcott-Rallison syndrome 4174 601656 Pancreatic agenesis and congenital heart defects 4173 600576 Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects 4195 138079 Permanent familial 3, 602485 28510 610192 Neonatal Diabetes mellitus with congenital hypothyroidism Autos omal domin ant Autos omal domin ant 304790 Rubio-Cabezas et al 2011 Diabetes 60:1349-1353 226980 Rubio-Cabezas et al 2009 94:4162-4170 600001 Lango Allen et al 2011 Nat Genet 44, 20-22 607941 614430 614429 ed Diabetes Phenoty pe MIM number from De Franco et al 2013 Diabetes 62, 993-997 Shaw-Smith et al 2014 Diabetes Apr 2 (Epub ahead of print) 606176 Njolstad et al 2001 N Engl J Med 344:1588-1592. 610199 Senee et al 2006 Nature Genetics 38:682-687, Dimitri et al 2011 EJE 164:437-443. intronic
HNF1 homeobox B (HNF1B) Pancreatic and duodenal homeobox 1 (PDX1) Neuronal differentiation 1 (NEUROD1) Neurogenin 3 (NEUROG3) Pancreas specific treanscription factor, 1a (PTF1A) NK2 homeobox 2 (NKX2.2) Regulatory factor X, 6 (RFX6) Solute carrier family 19 (thiamine transporter), member 2 (SLC19A2) 11630 189907 Transient neonatal diabetes 6107 600733 Permanent 7762 601724 Permanent and cerebellar agenesis 13806 604882 Permanent and enteric anendocrinosis 23734 607194 Permanent with cerebellar agenesis 7835 604612 21478 612659 Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities 10938 603941 Thiaminerespon megaloblastic anemia syndrome Yorifugi et al 2004 J Clin Endocrinol Metab 89:2905-2908. 260370 Stoffers et al 1997 Nat Genet 15:106-110, Thomas et al 2009 Pediatr Diabetes 10:492-496 Rubio-Cabezas et al 2010 Diabetes 59:2326-2331. 610370 Rubio-Cabezas et al 2011 Diabetes 60:1349-1353 609069 Sellick et al 2004 Nat Genet 36:1301-1315 and Weedon et al 2014 Nat Genet 46:61-64 Flanagan et al 2014 Cell Metab 19:146-154 601346 Spiegal et al 2011 AM J Med Genet 155:2821-2825, Smith et al 2010 Nature 463:775-780 249270 Shaw-Smith et al 2012 Pediatr Diabetes 13:314-321
Solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) Immediate early response 3 interacting protein 1 (IER3IP1) Motor neuron and pancreas homeobox 1 (MNX1) ZFP57 zinc finger protein Signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) 11006 138160 Fanconi-Bickel syndrome 18550 609382 Microcephaly, epilepsy and diabetes syndrome 4979 142994 18791 612192 Transient Neonatal Diabetes 11364 102582 Neonatal diabetes and additional multi-organ autoimmunity 227810 Sansbury et al 2012 Diabetologia 55:2381-2385 614231 Abdel-Salam et al 2012 Am J Med Genet 158:2788-2796 Flanagan et al 2014 Cell Metab 19:146-154 601410 Mackay et al 2008 Nat Genet 40:949-951 Flanagan et al 2014 Nature Genetics (In press)