ANALYSIS OF THE HNF1B GENE IN RENAL CYSTS AND DIABETES (RCAD)
The Renal Cysts And Diabetes (RCAD) syndrome is caused by heterozygous variants in the HNF1B gene (Bingham et al. 2000 Kidney Int 57:898-907; Edghill et al. 2006 J Med Genet 43:84-90). Whole gene deletions account for up to 50% of variants, and 40% of HNF1B variantsare de novo. An absence of family history of renal disease or diabetes should therefore not exclude genetic testing for RCAD.
Clinical presentations of RCAD usually include at least two of the following:
Neurodevelopmental disorders such as autism are observed in approximately 40% of patients with an HNF1B whole gene deletion occurring as part of a chromosome 17q12 microdeletion, but are not associated with HNF1B intragenic mutations (Clissold et al. 2016 Kidney Int 90: 203-211).
The severity of the renal phenotype is variable, from enlarged cystic kidneys incompatible with life to normal renal development and function, and HNF1B variants are a rare cause of diabetes in the absence of known renal disease (Edghill et al. 2013 Diabet Med 30:114-117).