Journal article

A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes

Joanne M Hildebrand, Bernice Lo, Sara Tomei, Valentina Mattei, Samuel N Young, Cheree Fitzgibbon, James M Murphy, Abeer Fadda



Maturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLK..

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Awarded by Australian National Health and Medical Research Council

Awarded by Australian Government NHMRC IRIISS

Funding Acknowledgements

This work has been funded by the internal Sidra Medicine research funding program, the Australian National Health and Medical Research Council (1058190) (J.M.H.) and 1172929 (J.M.M.), Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (9000653). Open access funding was provided by the Qatar National Library.