Coincidence of a novel KCNJ11 missense variant R365H with a paternally inherited 6q24 duplication in a patient with transient neonatal diabetes

  1. Juraj Staník, M.D1,2,
  2. Mark Lethby3,
  3. Sarah E. Flanagan, PhD4,
  4. Daniela Gašperíková, PhD1,
  5. Beata Milošovičová, M.D5,
  6. Margaret Lever6,
  7. Hilary Bullman6,
  8. Lejla Zubcevic3,
  9. Andrew T. Hattersley, M.D., F.R.C.P.4,
  10. Sian Ellard, PhD., M.R.C.Path4,
  11. Frances M. Ashcroft, D.Sc, PhD.3 and
  12. Iwar Klimeš, M.D., D.Sc (iwar.klimes{at}savba.sk)1
  1. 1DIABGENE and Diabetes Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia
  2. 2Children Diabetes Center at the 1st Department of Pediatrics Comenius University Medical School, Bratislava, Slovakia
  3. 3Department of Physiology, Anatomy and Genetics, University of Oxford, UK
  4. 4Institute of Biomedical and Clinical Research, Peninsula Medical School, Exeter, UK
  5. 5Diabetes Outpatient Clinic, Cyril and Method Hospital, Bratislava, Slovakia
  6. 6Salisbury Healthcare NHS Trust, District Hospital, Salisbury, UK

    Abstract

    Objective: Neonatal diabetes mellitus (NDM) is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent NDM are mutations of the KATP channel subunits; in transient NDM chromosome 6q24 abnormalities are the most common cause.

    History And Examination: We report a sporadic case of diabetes diagnosed on the 4th day of life without ketoacidosis.

    Investigations: Analysis of the KCNJ11 gene found a novel R365H mutation in the proband and her unaffected father. The functional analysis did not support pathogenicity of this variant. When the patient's diabetes remitted in the 7th month of life, the 6q24 region was analyzed and a paternally inherited duplication was identified.

    Conclusions: Our case reports a coincidental novel KCNJ11 variant in a patient with transient NDM due to a 6q24 duplication, illustrating the difficulty in testing neonates before the clinical course of NDM is known.

    Footnotes

      • Received March 18, 2008.
      • Accepted June 4, 2008.

    This Article

    1. Published online before print June 12, 2008, doi: 10.2337/dc08-0549
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