Endocrine Abstracts (2012) 28 P198

A novel genetic mutation causing MODY 1

Sally Brady & Mark Edwards


Diabeticare Unit, The Hillingdon Hospital, Uxbridge, United Kingdom.


Maturity-onset diabetes of the young (MODY) is a group of autosomal dominant inherited disorders causing non-insulin-dependent diabetes. MODY is the most common form of monogenic diabetes, accounting for 1-2 % of diabetes in Europe; however it is often misdiagnosed as Type 1 or 2 Diabetes. MODY is caused mainly by mutations in the GCK, HNF1A or HNF4A genes, the two former accounting for 70% of all cases. A molecular genetic diagnosis is important as it can directly alter patient management, e.g. HNF1A and HNF4A mutations respond very well to low dose sulphonylureas; whereas GCK mutations may require no treatment at all. Following diagnosis, family cascade screening may also be initiated. A novel case of MODY is described. The non-obese patient presented at 23 years with tiredness, polyuria and polydipsia. An OGTT was performed and the patient was diagnosed with T2DM by her GP based on the results. However, on referral to secondary care, the unusual presentation led to the suspicion of MODY. Molecular genetic analysis revealed a novel mutation in the P2 promoter region of the HNF4A gene (c.-174T>C; MODY1), believed to cosegregate with disease. Family cascade screening (glucose tolerance tests and molecular genetic testing) was initiated for first- and second-degree relatives. Glucose tolerance testing identified one sibling with diabetes and one with impaired glucose tolerance; both of which were subsequently shown to be positive for the novel HNF4A mutation on genetic testing.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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