一个遗传性腓骨肌萎缩症患者家系PMP22基因的杂合性重复分析

Analysis of heterozygous duplication of PMP22 gene in a pedigree affected with Charcot Marie Tooth disease

目的对遗传性腓骨肌萎缩症（Charcot-Marie-Tooth，CMT）患者家系进行PMP22基因的拷贝数分析，为患者提供病因诊断和遗传咨询。方法获取先证者及其父母、妻子的外周血DNA，从羊水中获取胎儿DNA，应用多重连接探针扩增技术对PMP22基因进行检测，异常结果用染色体微阵列分析技术和Sanger测序技术进一步分析。结果先证者及其父亲存在PMP22基因杂合性重复，二人PMP22基因外显子测序结果均无异常；未发现先证者母亲、妻子、胎儿PMP22基因拷贝数异常。先证者父亲无任何症状。结论先证者PMP22基因的杂合性重复导致CMT1A的发生。虽然cMT1A为常特体显性遗传病，但可能存在其他因素参与PMP22基因的表达调控。由于PMP22基因的不规则显性遗传性，为此类患者提供遗传咨询时要更加谨慎。

Objective To analyze mutation of the PMP22 gene in a pedigree affected with Charcot- Marie-Tooth disease. Methods Genomic DNA was extracted from peripheral blood samples of the proband and members from his family, and fetal DNA was extracted from amniotic fluid sample. Multiplex ligation- dependent probe amplification （MLPA） and array-based comparative genomic hybridization （array-CGH） analyses were carried out to determine the copy number of the PMP22 gene. Sanger sequencing was carried out to detect point mutations of the PMP22 gene. Results A heterozygous duplication of the PMP22 gene was detected in the proband and his father, while no point mutation, insertion or deletion was found in them. No duplication or deletion of the PMP22 gene was found in other family members. Conclusion Based on clinical symptoms and genetic findings, the heterozygous duplication of the PMP22 gene is probably the cause of the disease in the proband. The fact that the father has carried the same duplication hut with no detectable symptom may be due to irregular transmission pattern of the mutation. Genetic counseling for the family should therefore be with caution.