一例COMP基因杂合突变致假性软骨发育不全病例

A case of pseudochondroplasia caused by a heterozygous mutation in the COMP gene

目的 对假性软骨发育不全(PSACH)确诊患儿及其家系成员进行软骨寡聚基质蛋白(COMP)基因检测,并进行分析。方法 采集患儿及父母清晨空腹外周静脉血各5 mL,抽取基因组DNA,进行PCR扩增,采用高通量测序方式读出原始测序数据;同时,对于致病突变基因所在片段上下游设计引物,进行PCR扩增,对产物行Sanger测序。结果 患儿存在杂合突变c.1048_1116del(exon 10,NM_000095),导致氨基酸发生整码突变(p.N350_D372del)。患儿父母均未检测出COMP基因突变位点。结论 COMP基因第10外显子杂合突变c.1048_1116del(exon 10,NM_000095)为PSACH的致病突变,在国内外PSACH患者中属于首次发现。患儿父母外周血基因正常,提示其父母可能与该突变的生殖腺嵌合体有关。

Objective To analyze the children diagnosed with pseudo achondroplasia(PSACH) and their family members for cartilage oligomeric matrix protein(COMP) gene testing. Methods Collect 5 mL of fasting peripheral venous blood from children and their parents in the morning, extract genomic DNA, PCR amplification, high-throughput sequencing,primers were designed upstream and downstream of the segment where the pathogenic mutation gene, PCR amplification and the products were Sanger sequencing. Results The heterozygous mutation c.1048_1116del(exon 10, NM_000095), resulting in the encoding of the amino acid mutation(p.N350_D372del). No pediatric parents detected any mutation sites in the COMP gene. Conclusion The heterozygous mutation c.1048_1116del(exon 10, NM_000095) of the COMP gene is a pathogenic mutation of PSACH, which is the first discovery in PSACH patients at home and abroad, and may be related to the occurrence of PSACH. The pediatric parents had normal peripheral blood genes, suggesting that the parents may be associated with the gonad chimera of this mutation.