Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel
Gloyn, Anna L., Cummings, Elizabeth A., Edghill, Emma L., Harries, Lorna W., Scott, Rachel, Costa, Teresa, Temple, Karen, Hattersley, Andrew T. and Ellard, Sian (2004) Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel. Journal of Clinical Endocrinology & Metabolism, 89, (8), 3932-3935.
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Description/Abstract
Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the beta-cell ATP-sensitive potassium channel have recently been shown to be a common cause of permanent neonatal diabetes. In 80% of probands, these are isolated cases resulting from de novo mutations. We describe a family in which two affected paternal half-siblings were found to be heterozygous for the previously reported R201C mutation. Direct sequencing of leukocyte DNA showed that their clinically unaffected mothers and father were genotypically normal. Quantitative real-time PCR analysis of the father's leukocyte DNA detected no trace of mutant DNA. These results are consistent with the father being a mosaic for the mutation, which is restricted to his germline. This is the first report of germline mosaicism in any form of monogenic diabetes. The high percentage of permanent neonatal diabetes cases due to de novo KCNJ11 mutations suggests that germline mosaicism may be common. The possibility of germline mosaicism should be considered when counseling recurrence risks for the parents of a child with an apparently de novo KCNJ11 activating mutation.
| Item Type: | Article |
|---|---|
| ISSN: | 0021-972 (print) |
| Uncontrolled Keywords: | humans, germ-line mutation, mutation, adenosine triphosphate, mutation, potassium, gene expression regulation, arginine, cysteine, diabetes mellitus, child, heterozygote, non-U.S.gov't, fathers, counseling,inwardly rectifying, male, pedigree, infant, blood, risk, genetics,newborn,adenosine, mothers, parents, potassium channels, recurrence, dna, islets of langerhans, alleles, research support, report, missense, mosaicism, analysis, family, potassium channels, metabolism, diabetes |
| Related URLs: | http://jcem.endojournals.org/c.../89/8/3932 |
| Subjects: | R Medicine Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine |
| ePrint ID: | 59758 |
| URI: | http://eprints.soton.ac.uk/id/eprint/59758 |
| Deposited On: | 04 Sep 2008 |
| Last Modified: | 01 Jun 2011 01:38 |
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