, Volume 54, Issue 8, pp 2202-2205
Date: 21 May 2011

The previously reported T342P GCK missense variant is not a pathogenic mutation causing MODY

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To the Editor:

There is renewed interest in the difficulties of interpreting the role of missense variants identified in large scale medical resequencing projects made possible by next generation sequencing technologies. To assist in ascribing a role in disease causation for these variants, a combination of statistics, bioinformatic tools and, ultimately, functional studies, will be needed. Missense variants identified in highly penetrant Mendelian disorders where co-segregation studies can be performed provide a model to explore the utility of these tools. Fig. 1

Partial pedigrees showing status of (a) family SQ and (b) family GB. Affected (fully shaded), mild hyperglycaemia present (grey shading), unaffected (no shading). N/N indicates no mutation found. Arrow indicates proband. Current age for normoglycaemic participants provided and age at hyperglycaemia diagnosis provided for others; current BMI and current glycaemic status provided. BG, blood glucose; FPG, fasting plasma glucose; G ...

A. L. Gloyn and S. Ellard contributed equally to this study.