Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 yr of age. Issue 2 (10th September 2012)

• Record Type: Journal Article
• Authors: Moritani, Maki; Yokota, Ichiro; Tsubouchi, Kohji; Takaya, Ryuzo; Takemoto, Koji; Minamitani, Kanshi; Urakami, Tatsuhiko; Kawamura, Tomoyuki; Kikuchi, Nobuyuki; Itakura, Mitsuo; Ogata, Tsutomu; Sugihara, Shigetaka; Amemiya, Shin
• Is Part Of: Pediatric diabetes. Volume 14:Issue 2(2013)
• Page Start: 112
• Page End: 120
• Publication Date: 2012-09-10
• Subjects: Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/j.1399-5448.2012.00917.x
• Languages: English
• ISSNs: 1399-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pedi917-sec-0001" sec-type="section"> <title>Background</title> <p>The etiology of type 1 diabetes (T1D) is heterogeneous and is according to presence or absence of pancreatic autoantibodies divided into two subtypes: type 1A (autoimmune‐mediated) and type 1B (non‐autoimmune‐mediated). Although several genes have been linked to type 1A diabetes, the genetic cause of type 1B diabetes in Japanese individuals is far from understood.</p> </sec> <sec id="pedi917-sec-0002" sec-type="section"> <title>Objective</title> <p>The aim of this study was to test for monogenic forms of diabetes in auto antibody‐negative Japanese children with T1D.</p> </sec> <sec id="pedi917-sec-0003" sec-type="section"> <title>Methods</title> <p>Thirty four (19 males and 15 female) unrelated Japanese children with glutamate decarboxylase (GAD) 65 antibodies and/or IA‐2A‐negative T1D and diabetes diagnosed at < 5 yr of age were recruited from 17 unrelated hospitals participating in the <italic>J</italic>apanese <italic>S</italic>tudy <italic>G</italic>roup of <italic>I</italic>nsulin <italic>T</italic>herapy for children and adolescent diabetes (JSGIT). We screened the <italic>INS</italic> gene and the <italic>KCNJ11</italic> gene which encode the ATP‐sensitive potassium cannel by direct sequencing in 34 Japanese children with T1D.</p> </sec> <sec id="pedi917-sec-0004" sec-type="section"> <title>Results</title> <p>We identified three novel (C31Y, C96R, and C109F) mutations and one previously reported mutation (R89C) in the <italic>INS</italic> gene in five children, in addition to one mutation in the <italic>KCNJ11</italic> gene (H46R) in one child. These mutations are most likely pathogenic and therefore the cause of diabetes in carriers.</p> </sec> <sec id="pedi917-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Our results suggest that monogenic forms of diabetes, particularly <italic>INS</italic> gene mutations, can be detected in Japanese patients classified with type 1B. Mutation screening, at least of the <italic>INS</italic> gene, is recommended for Japanese patients diagnosed as autoantibody negative at <5 yr of age.</p> </sec> </abstract>