Abstract：
CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.
摘要：
CHST3相关的软骨发育不良伴先天性关节脱位（CDCJD，#MIM143095),是一种罕见的遗传性骨骼疾病，由CHST3中功能变异的双等位基因丧失引起。CHST3对于硫酸软骨素的硫酸化至关重要。本研究描述了9例具有CDCJD主要症状的患者的临床表现；先天性关节（膝关节和肘关节）脱位，短躯干短身材进行性椎体异常，掌骨缩短.其他表现包括不规则的股骨远端骨phy，多余的腕骨骨化中心，肱骨两裂,球杆脚,和心脏异常。进行Sanger测序以研究8例患者的分子病因，并对1例患者进行外显子组测序。遗传测试揭示了CHST3中的五个纯合变体（四个是新的，一个是以前报道的）。所有这些变体位于CHST3蛋白的磺基转移酶结构域上,并且被分类为致病性/可能致病性。因此，我们报告了来自印度的9例与CHST3相关的软骨发育不良伴先天性关节脱位的患者，并建议在这种情况下监测心脏瓣膜的健康状况。
