Novel COMP Mutation

We recruited an AD-MED family with 10 affected members and 17 unaffected members. The main radiographic findings were symmetrical changes in the dysplastic acetabulum and femoral heads, irregular contours of the epiphyses, a shortened femoral neck, and flatfoot. Lower bone density was also observed in the ankle joints, wrist joints, and knees, as well as irregular vertebral end plates. In the proband, we identified the missense mutation c.1153G>T (p. Asp385Tyr), located in exon 11 of the COMP gene. This mutation was assessed as “pathogenic” because of its low allele frequency and its high likelihood of co-segregation with disease in the reported family. Sanger sequencing identified the novel heterozygous mutation c.1153G>T (p. Asp385Tyr) in exon 11 of COMP in all affected individuals in the family.

本研究招募了一个AD-MED家族，其中包含10名受影响的成员和17名未受影响的成员。主要的放射学表现为髋臼发育不良的对称性改变、干骺端的轮廓不规则、股骨颈缩短和平足。此外，在踝关节、腕关节和膝关节中也观察到较低的骨密度，以及椎体终板的异常。在先证者中，我们鉴定出位于COMP基因第11外显子的错义突变c.1153G>T（p.Asps385Tyr）。由于该突变具有较低的等位基因频率及其与报道的家族疾病共分离的高可能性，因此被评估为“致病性”。Sanger测序在家族中所有受影响的个体中均检测到位于COMP基因第11外显子的新发杂合突变c.1153G>T（p.Asps385Tyr）。