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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.

Original publication




Journal article


J Clin Endocrinol Metab

Publication Date





3932 - 3935


Adenosine Triphosphate, Alleles, Arginine, Cysteine, DNA, Diabetes Mellitus, Fathers, Gene Expression Regulation, Germ-Line Mutation, Heterozygote, Humans, Infant, Newborn, Islets of Langerhans, Male, Mosaicism, Mutation, Missense, Pedigree, Potassium Channels, Inwardly Rectifying