Spondyloepiphyseal dysplasia Omani type: CHST3 mutation spectrum and phenotypes in three Indian families

We describe three consanguineousIndian families with a distinct form of spondyloepiphyseal dysplasia( SEDOmani type). It is an autosomal recessive disorder due to mutation in CHST3 gene. CHST3 gene encodes the enzyme chondroitin6-O- sulfotransferase-1 (C6ST-1) which mediates the sulfation of proteoglycans, ( chondroitin sulfate), in the extracellular matrix of cartilage. CHST3 gene was sequenced in probands from three different families with SED. In two families missense mutations (c.904G>C predicting the substitution D302H) and c.491C>T (P164L) were identified. A frameshift (insertion) mutation (c.533_534ins G predicting the substitution A179Rfs*) was found in the third family. SNP micrarray in the family 2 helped to localize the common areasof homozygosity and identified the candidate gene. The confirmation by molecular diagnosis will be useful in the management and in the counseling of affected patients and their families. The presence of sclerosis of cranial suturesadds to the phenotypic spectrum of the disorder. Severe cardiac valvular disease in a case and triangular epiphyses of knees are other features which are highlighted in this report. © 2016 Wiley Periodicals, Inc.