BACKGROUND/ OBJECTIVE: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. METHODS: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. RESULTS: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. CONCLUSIONS: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.
BACKGROUND/ OBJECTIVE: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. METHODS: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. RESULTS: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. CONCLUSIONS: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.
Authors: R J Gardner; D J Mackay; A J Mungall; C Polychronakos; R Siebert; J P Shield; I K Temple; D O Robinson Journal: Hum Mol Genet Date: 2000-03-01 Impact factor: 6.150
Authors: Anna L Gloyn; Elizabeth A Cummings; Emma L Edghill; Lorna W Harries; Rachel Scott; Teresa Costa; I Karen Temple; Andrew T Hattersley; Sian Ellard Journal: J Clin Endocrinol Metab Date: 2004-08 Impact factor: 5.958
Authors: Jørn V Sagen; Helge Raeder; Eba Hathout; Naim Shehadeh; Kolbeinn Gudmundsson; Halvor Baevre; Dianne Abuelo; Chanika Phornphutkul; Janne Molnes; Graeme I Bell; Anna L Gloyn; Andrew T Hattersley; Anders Molven; Oddmund Søvik; Pål R Njølstad Journal: Diabetes Date: 2004-10 Impact factor: 9.461
Authors: Anna L Gloyn; Ewan R Pearson; Jennifer F Antcliff; Peter Proks; G Jan Bruining; Annabelle S Slingerland; Neville Howard; Shubha Srinivasan; José M C L Silva; Janne Molnes; Emma L Edghill; Timothy M Frayling; I Karen Temple; Deborah Mackay; Julian P H Shield; Zdenek Sumnik; Adrian van Rhijn; Jerry K H Wales; Penelope Clark; Shaun Gorman; Javier Aisenberg; Sian Ellard; Pål R Njølstad; Frances M Ashcroft; Andrew T Hattersley Journal: N Engl J Med Date: 2004-04-29 Impact factor: 91.245
Authors: P R Njølstad; O Søvik; A Cuesta-Muñoz; L Bjørkhaug; O Massa; F Barbetti; D E Undlien; C Shiota; M A Magnuson; A Molven; F M Matschinsky; G I Bell Journal: N Engl J Med Date: 2001-05-24 Impact factor: 91.245
Authors: Martine Vaxillaire; Céline Populaire; Kanetee Busiah; Hélène Cavé; Anna L Gloyn; Andrew T Hattersley; Paul Czernichow; Philippe Froguel; Michel Polak Journal: Diabetes Date: 2004-10 Impact factor: 9.461
Authors: Brian W Thurber; David Carmody; Elizabeth C Tadie; Ashley N Pastore; Jazzmyne T Dickens; Kristen E Wroblewski; Rochelle N Naylor; Louis H Philipson; Siri Atma W Greeley Journal: Diabetologia Date: 2015-04-17 Impact factor: 10.122
Authors: Siri Atma W Greeley; Susan E Tucker; Rochelle N Naylor; Graeme I Bell; Louis H Philipson Journal: Trends Endocrinol Metab Date: 2010-04-29 Impact factor: 12.015
Authors: David B Sacks; Mark Arnold; George L Bakris; David E Bruns; Andrea Rita Horvath; M Sue Kirkman; Ake Lernmark; Boyd E Metzger; David M Nathan Journal: Diabetes Care Date: 2011-06 Impact factor: 19.112
Authors: Roopa Kanakatti Shankar; Catherine Pihoker; Lawrence M Dolan; Debra Standiford; Angela Badaru; Dana Dabelea; Beatriz Rodriguez; Mary Helen Black; Giuseppina Imperatore; Andrew Hattersley; Sian Ellard; Lisa K Gilliam Journal: Pediatr Diabetes Date: 2012-10-10 Impact factor: 4.866
Authors: Ming Liu; Leena Haataja; Jordan Wright; Nalinda P Wickramasinghe; Qing-Xin Hua; Nelson F Phillips; Fabrizio Barbetti; Michael A Weiss; Peter Arvan Journal: PLoS One Date: 2010-10-11 Impact factor: 3.240
Authors: Janani Kumaraguru; Sarah E Flanagan; Siri Atma W Greeley; Roos Nuboer; Julie Støy; Louis H Philipson; Andrew T Hattersley; Oscar Rubio-Cabezas Journal: Diabetes Care Date: 2009-05-12 Impact factor: 19.112