Spondyloepiphyseal dysplasia, Omani type: Further definition of the phenotypeHow to cite this article: van Roij MHH, Mizumoto S, Yamada S, Morgan T, TanSindhunata MB, MeijersHeijboer H, Verbeke JILM, Markie D, Sugahara K, Robertson SP. 2008. Spondyloepiphyseal dysplasia, Omani type: Further definition of the phenotype. Am J Med Genet Part A 146A:2376–2384.M.H.H. van Roij and S. Mizumoto contributed equally to this work.

Spondyloepiphyseal dysplasia SED, Omani type OMIM 608637 is a recessively inherited skeletal dysplasia previously described in two distantly related families from the Republic of Oman. The phenotype consists of short stature, severe kyphoscoliosis, arthritic joints elbows, wrists, knees, secondary large joint dislocations, rhizomelia, fusion of carpal bones and mild brachydactyly. Affected individuals were homozygous for a missense mutation, R304Q in CHST3that encodes the enzyme chondroitin 6Osulfotransferase1 C6ST1. This enzyme mediates the sulfation of proteoglycans, particularly chondroitin sulfate CS, in the extracellular matrix of cartilage. Here we describe the identification of a mutation 857T > C predicting the substitution L286P in CHST3in a Turkish family and extend the clinical phenotype of SEDOmani type to include congenital joint dislocation, club feet, ventricular septal defect, deafness, metacarpal shortening and accessory carpal ossification centers. Fibroblasts and urine obtained from affected patients demonstrated negligible levels of 6Osulfated GalNAc residue in CS. Furthermore, the 6Osulfotransferase activity of cloned C6ST1 into which the L286P mutation had been introduced was dramatically reduced, confirming the pathogenicity of this substitution. These results indicate that the clinical consequences of a deficiency of 6Osulfation in CS can be varied and that a clinical spectrum may exist similar to that seen in other skeletal dysplasias characterized by disorders of proteoglycan sulfation. © 2008 WileyLiss, Inc.