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Abstract：
We describe three consanguineous Indian families with a distinct form of spondyloepiphyseal dysplasia (SED Omani type). It is an autosomal recessive disorder due to mutation in CHST3 gene. CHST3 gene encodes the enzyme chondroitin 6-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 areas of 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 sutures adds 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.
摘要：
我们描述了三个近亲的印度家庭，这些家庭具有明显的脊柱骨发育不良（SED阿曼型）。它是由于CHST3基因突变引起的常染色体隐性遗传疾病。CHST3基因编码软骨素6-O-磺基转移酶-1（C6ST-1），该酶介导蛋白聚糖的硫酸化，（硫酸软骨素），在软骨的细胞外基质中。在来自三个不同SED家庭的先证者中对CHST3基因进行了测序。在两个家庭中，鉴定了错义突变（c.904G>C预测取代D302H）和c.491C>T（P164L）。在第三个家族中发现了移码（插入）突变（c.533_534insG，预测取代A179Rfs*）。家族2中的SNP微阵列有助于定位纯合性的共同区域并鉴定候选基因。分子诊断的确认将有助于受影响的患者及其家人的管理和咨询。颅骨缝合线硬化的存在增加了该疾病的表型谱。严重的心脏瓣膜疾病和膝盖的三角形骨phy是本报告中强调的其他特征。©2016威利期刊，Inc.
