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Familial Nephropathy and Multiple Exostoses With Exostosin-1 (EXT1) Gene Mutation

Ian S.D. Roberts ^*1 and Jonathan M. Gleadle

*Department of Cellular Pathology, John Radcliffe Hospital, Headley Way, Headington, Oxford, United Kingdom; and Renal Unit, Level 6, Flinders Medical Centre, Bedford Park, South Australia, Australia

¹ To whom correspondence should be addressed. E-mail: ian.roberts{at}orh.nhs.uk.

	Abstract

Glomerular deposition of fibrillar collagen is a characteristic finding of genetically distinct conditions, including nail-patella syndrome and collagen type III glomerulopathy. A case of familial nephropathy in which steroid-sensitive nephrotic syndrome and glomerular deposits of fibrillar collagen are associated with multiple exostoses due to mutation of the EXT1 gene is described. This gene encodes a glycosyltransferase required for synthesis of heparan sulfate glycosaminoglycans. There is deficiency of heparan sulfate and perlecan, together with accumulation of collagens, in the matrix of EXT1-associated osteochondromas. Similar glomerular basement membrane abnormalities could offer an explanation for both the renal ultrastructural changes and steroid-sensitive nephrotic syndrome.