肯尼迪病3个家系的临床、基因型和遗传特征分析

Study on clinical manifestation,genotype and pedigree characteristics of three pedigrees with Kennedy disease

目的分析3个肯尼迪病（Kennedy disease,KD）家系的临床、基因及遗传特征。方法收集3个KD家系患者的详细病史、体格检查、血生化及电生理检查等资料,用基因分析的方法测定先证者及家族成员雄性激素受体（androgen receptor,AR）基因的CAG重复序列拷贝数。结果 3个家系发现的5例KD患者主要临床表现为四肢肌肉萎缩、无力和肢体震颤,舌肌萎缩、纤颤;实验室检查发现肌酸激酶升高;肌电图检查可见失神经电位;神经传导速度检查提示感觉神经受损。KD患者AR基因CAG重复次数在42～49。3个家系的遗传方式符合X连锁隐性遗传。结论 KD主要影响男性患者,病情缓慢进展,主要表现为脊髓和延髓肌肉的萎缩和无力。基因检测有助确诊,并可检测出携带者,以进行家系遗传分析。

Objective To study the clinical,genetic and hereditary characteristics of three pedigrees with Kennedy disease（KD）.Methods The clinical data,including case history,physical examination,biochemical analysis of blood,electromyography（EMG）and nerve conduction velocity（NCV）of three pedigrees with KD were collected.The number of CAG repeat region copies in androgen receptor（AR）gene were determined by PCR and DNA sequencing among the proband and family members.Results The clinical characteristics of the 5 patients included atrophy of lingualis,fibrillation,limbs muscular atrophy, weakness and limb tremor.Laboratory examination showed the levels of serum creatine kinase（CK） were elevated,EMG showed denervation motor potentials and NCV showed the damage of sensory nerve in all cases.The number of（CAG）n repeats in AR gene was 42-49,respectively.X-linked recessive mode of inheritance was demonstrated by pedigree analysis in the three families.Conclusions KD mainly affects the males,shows a slowly progressing spinal and bulbar muscular atrophy.Genetic analysis contributes to diagnosis and identification of carriers,and is beneficial to the pedigree analysis research.