Novel ABCC8 (SUR1) Gene Mutations in Asian Indian Children with Congenital Hyperinsulinemic Hypoglycemia |
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| Authors: | Suresh Jahnavi Varadarajan Poovazhagi Sekar Kanthimathi Kandasamy Balamurugan Dhanasekaran Bodhini Jaivinder Yadav Vandana Jain Rajesh Khadgawat Mahuya Sikdar Ayurchelvan Bhavatharini Ashok Kumar Das Tanvir Kaur Viswanathan Mohan Venkatesan Radha |
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| Affiliation: | 1. Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Type 2 Diabetes and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non‐Communicable Diseases Prevention & Control, IDF Centre of Education, Gopalapuram, , Chennai, India;2. Institute of Child Health and Hospital for Children, , Chennai, India;3. All India Institute of Medical Sciences, , New Delhi, India;4. SRC Diabetes Care Centre, , Erode, India;5. Jawaharlal Institute of Postgraduate Medical Education and Research, , Puducherry, India;6. Indian Council of Medical Research, , New Delhi, India |
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| Abstract: | Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β‐cell ATP‐sensitive K+ channel (KATP channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide. Dominant KATP mutations have been associated with diazoxide‐responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed by sequence analysis in 22 children with congenital HI. We found 10 novel mutations (c.1delA, c.61delG, c.267delT, c.619–629delCCCGAGGACCT, Gln444*, Leu724Pro, Ala847Thr, Trp898*, IVS30–2A>C, and Leu1454Arg) and two known mutations (Gly111Arg and Arg598*) in the ABCC8 gene. This study describes novel and known ABCC8 gene mutations in children with congenital HI. This is the first large genetic screening study on HI in India and our results will help clinicians in providing optimal treatment for patients with hyperinsulinemia and in assisting affected families with genetic counseling. |
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| Keywords: | KCNJ11 gene ABCC8 gene GLUD1 gene hyperinsulinemia |
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