Ⅱ型常染色体显性遗传骨硬化症一个家系的临床和遗传学分析

Clinical and genetic analysis of a Chinese family with autosomal dominant osteopetrosisⅡ

目的检测常染色体显性遗传性骨硬化症一个家系氯离子通道7(chloride channel 7,CLCN7)基因的突变情况。方法收集一骨硬化症家系中2例患者及先证者父母共4人的血液标本,提取基因组DNA,用PCR扩增CLCN7外显子并对所有外显子进行测序分析。结果 2例患者及先证者父亲均存在CLCN7第10号外显子856位核苷酸C变成T,导致286位的精氨酸(Arg)被色氨酸(Trp)代替(R286W),为一已知突变;先证者母亲无此突变。存在CLCN7突变的3人临床表现不同,提示该遗传疾病存在外显不全。结论 CLC7 R286W突变是导致该家系骨硬化症的致病原因。

Objective To characterize the mutation of CLCN7 gene in a Chinese family with autosomal domi- nant osteopetrosis Ⅱ （ ADOⅡ）. Methods Genomic DNA was extracted from peripheral blood samples of two patients and the parents of one patient. Polymerase chain reaction （PCR） was used to amplify the exons of CLCN7. Then the PCR product was sequenced to detect the mutation. Results A heterozygous missense mutation （C856T） in exon 10 of CLCN7 was detected in two patients and the father of one patient. This mutation resulted in the substitution of Trp residue for Arg at the position 286 of CLC7 protein, which had been reported in ADO Ⅱ patients. The clinical phenotype of the three carriers was different. Conclusion These two Chinese ADO Ⅱ patients were resulted from the R286W mutation in CLC7 protein.