一例Ⅱ型常染色体显性骨硬化症患者CLCN7基因突变分析

Objective To investigate the mutation status of the chloride channel 7 gene (CLCN7) in a patient with type II autosomal dominant osteopetrosis (ADO). Methods A young female patient with osteopetrosis was included. Clinical manifestations were analyzed by clinical means such as bone mineral density detection and X-ray imaging; exon sequencing of the CLCN7 gene was performed on the patient and her father, and exon sequencing of the CLCN7 gene was carried out on 50 samples randomly selected from a normal human DNA sample bank for comparative analysis of the sequencing results. Results The X-ray film showed an increase in vertebral bone mineral density, presenting a "sandwich" appearance; an increase in bone mineral density in the hip and femur, and a "bone within a bone" phenomenon in the pelvis. The bone mineral density results showed that the Z-score of lumbar vertebrae 1 - 4 was 13, the Z-score of the femoral neck was 7.8, and the Z-score of the total hip was 10. The patient's bones showed osteopetrosis manifestations. The sequencing results showed a missense mutation (homozygous mutation) on exon 9, resulting in c.746C>T (p.Pro249Leu); neither her father nor the 50 control samples had this mutation. Conclusion This patient has ADO type II autosomal dominant osteopetrosis with a homozygous missense mutation of c.746C>T (p.Pro249Leu) in the CLCN7 gene.

目的探讨1例Ⅱ型常染色体显性遗传骨硬化症(autosomal dominant osteopetrosis,ADO)患者的氯离子通道7基因(chloride channel 7,CLCN7)的突变情况。方法纳入1例骨硬化青年女性患者。采用骨密度检测、X线成像等临床手段对其临床表现进行分析;并对患者及其父亲的CLCN7基因进行外显子测序,从正常人DNA样本库中随机挑选50个样本进行CLCN7基因外显子测序来对比分析测序结果。结果X线片显示椎体骨密度增加,成“夹心饼”样;髋部和股骨骨密度增加,盆骨出现“骨中骨”现象。骨密度结果显示腰椎1-4 Z值为13,股骨颈Z值为7.8,全髋Z值为10,患者骨骼呈骨硬化表现,测序结果显示9号外显子上发生错义突变(纯合突变),导致c.746C>T(p.Pro249Leu);其父亲和50个对照样本均无此突变。结论此患者为CLCN7基因c.746C>T(p.Pro249Leu)纯合错义突变的ADO Ⅱ型常染色体显性骨硬化症。