CLCN 7基因突变致Ⅱ型常染色体显性遗传性骨硬化症1例报告并文献复习

MUTATION IN THE CLCN7 GENE CAUSING AUTOSOMAL DOMINANT OSTEOPETROSIS TYPEⅡ:A CASE REPORT AND LITERATURE REVIEW

目的对1例Ⅱ型常染色体显性遗传性骨硬化症(autosomal dominant osteopetrosis disease typeⅡ,ADOⅡ)患者的CLCN 7基因的突变位点进行分析,以提高临床上对该病的认识。方法收集1例ADOⅡ患者的临床资料,并采集该患者及其妻子和女儿的外周静脉血,应用PCR方法扩增CLCN 7基因的外显子,将扩增出的PCR产物纯化测序筛选突变位点。结果患者左下后牙区肿痛,抗炎治疗效果不佳。入院后全麻下行左下颌骨骨髓炎刮治术并死骨摘除术,术中将左下颌骨病变区肉芽组织及死骨送检,病理诊断示(下颌骨骨髓)慢性化脓性炎伴肉芽组织增生、下颌骨死骨形成。基因检测显示该例患者CLCN 7基因第24外显子错义突变,即p.Arg743Trp突变。术后给予补液、抗感染治疗,出院时患者一般情况良好,左下颌区无肿痛,口内切口无渗血,愈合良好。结论CLCN 7基因p.Arg743Trp错义突变可导致ADOⅡ。可为本地区ADOⅡ人群今后在基因层面的诊断和治疗提供参考依据。

Objective To analyze the mutation in the CLCN7 gene in a patient with autosomal dominant osteopetrosis typeⅡ(ADOⅡ),and to improve clinical understanding of the disease.Methods The clinical data of a patient with ADOⅡwere collected,and the peripheral blood samples of the patient and his wife and daughter were collected.The exons in the CLCN7 gene were amplified using polymerase chain reaction(PCR).The products from the PCR amplification were purified,sequenced,and screened for mutation sites.Results The patient’s lower left posterior tooth region was swollen and painful,and the effect of anti-inflammatory treatment was not satisfactory.After admission,a curettage surgery for the left mandibular osteomyelitis combined with dead bone removal was performed under general anesthesia.During the surgery,the granulation tissue and dead bones in the left mandible diseased area were submitted for examination.The pathological diagnosis showed(mandibular bone marrow)chronic suppurative inflammation with granulation tissue proliferation and dead bone formation in the mandible.Gene testing revealed a missense mutation in exon 24 of the CLCN7 gene,namely the p.Arg743Trp mutation.After surgery,fluid infusion and anti-infective treatment were given.Upon discharge,the patient had a good general condition,with no swelling or pain in the left mandibular area;the incisions in the mouth healed well,and showing no bleeding.Conclusion The missense mutation of p.Arg743Trp in the CLCN 7 gene can lead to ADOⅡ.This study can provide reference for genetic diagnosis and treatment of ADOⅡin the local population in the future.