基因检测确诊一例肯尼迪病及其家系的调查分析

Investigation of a family with Kennedy disease by genetic analysis

目的对1例临床疑似肯尼迪病的患者及其家系成员进行雄激素受体基因（androgenreceptor，AR）变异分析以明确病因，并阐明其临床特征和分子生物学特点。方法收集患者的临床资料，对患者及其家系共7名成员的AR基因第1外显子cAG重复序列进行基因检测，同时检测相关生化指标，分析临床表型。结果先证者进行性四肢近端肌肉无力、震颤、萎缩，伴乳房女性化、性功能减退、肌酶增高；肌电图显示感觉、运动神经均受累。经基因检测检出先证者AR基因CAG重复数为43，两名女性成员等位基因上的cAG重复数分别为22／43和23／43，另有两名男性成员CAG重复数分别为42和43，其中一名成年男性有与先证者类似的临床症状。结论经基因检测疑似患者确诊为肯尼迪病，家系中发现另外两名男性受累者和两名女性携带者。

Objective To report on a Chinese family from Wenzhou with genetically confirmed Kennedy disease and describe its clinical and genetic features. Methods The clinical phenotype and the level of relevant biochemical markers were assessed. To determine the number of CAG repeats in the exon 1 of androgen receptor （AR） gene, genomic DNA was extracted from peripheral blood samples of the family members, amplified by PCR and identified by DNA sequencing. Results The proband showed predominantly proximal limb weakness, fasciculation, muscle atrophy, gynecomastia, sexual dysfunction and increased serum creatine kinase. Myopathy and neuropathy were identified by electromyography. Two other affected males and 2 affected female carriers were identified to carry an expanded CAG repeat in the AR gene. The numbers of CAG repeats were found to be 43 in the proband, 43 and 42 in the other two affected males, one of which had similar clinical symptoms to the proband. Conclusion The family was diagnosed with Kennedy disease by analysis of the AR gene.