摘要目的 对Kennedy病家系进行临床表型和雄激素受体(androgen receptor,AR)基因突变分析.方法 收集Kennedy病家系2例患者和6例家系成员,对先证者进行神经系统查体,常规检测神经电生理、肌电图、血清肌酸激酶(creatine kinase,CK).抽取8例样本的外周静脉血,提取基因组DNA,PCR扩增AR基因第1号外显子中的CAG重复片段,PCR产物经1.5％琼脂糖凝胶电泳,男性样本进行DNA直接测序.通过毛细胞电泳片段分析技术明确患者及家系成员AR基因第1外显子CAG序列的重复数.结果 2例患者肌电图均显示感觉、运动神经受累及,血清CK均增高,经AR基因CAG重复序列分析,2例患者(Ⅲ1和Ⅲ3)CAG的重复数分别为58次和54次,并检出了4例女性携带者(Ⅱ1、Ⅱ3、Ⅲ5和Ⅳ1),Ⅱ1携带者CAG的重复数为22/58次,Ⅱ3携带者CAG的重复数为22/54次,Ⅲ5携带者CAG的重复数为24/54次,Ⅳ5携带者CAG的重复数为20/61次,2例表型正常男性成员的CAG的重复数均为24次.结论 CAG重复在本家系中存在不稳定遗传.基因诊断可作为Kennedy病诊断的可靠依据.Kennedy病患者进行AR基因突变检测可帮助家系成员进行遗传咨询,对该病的治疗和预防有重要意义.

abstractsObjective To identify the androgen receptor (AR) gene mutation in a pedigree with Kennedy disease.Methods Two Kennedy disease probands and six family members were collected.Routine detections including neurological examination,neurophysiological EMG and serum creatine kinase (CK) were preformed for two probands.Genomic DNA from eight peripheral venous blood samples was extracted.The repeat numbers of the trinucleotide CAG tandem-repeat in exon 1 of the AR gene were detected by polymerase chain reaction (PCR) amplification.PCR product was confirmed by 1.5 ％ agarose gel electrophoresis,and abnormal samples were detected by DNA direct sequencing.The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by capillary electrophoresis fragment analysis.Results EMG results of two probands showed that sensory and motor nerves were involved and serum CK was increased.The repeat numbers of the trinucleotide CAG tandem-repeat in exon 1 of the androgen receptor gene of two patients (Ⅲ 1 and Ⅲ3) were 58 and 54,respectively.Four female carriers (Ⅱ 1,Ⅱ 3,Ⅲ5 and Ⅳ 1) were found.The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅱ 1 carrier were 22 and 58.The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅱ 3 carrier were 2 2 and 5 4.The repeat numbers of the trinueleotide CAG tandem-repeat of Ⅲ 5 carrier were 24 and 54.The repeat numbers of the trinucleotide CAG tandem-repeat of Ⅳ 1 carrier were 20 and 61.The repeat number of the trinucleotide CAG tandem-repeat of two normal male samples was 24.Conclusion The repeat number of the trinucleotide CAG tandem-repeat of the family was unstable.Gene diagnosis can be used as a reliable basis for the diagnosis of Kennedy disease.AR gene mutation detection can help the family genetic counseling.It has important significance for the treatment and prevention of Kennedy disease.