Kennedy病两个家系的临床表型、基因型和遗传特征分析

目的 分析两个Kennedy病家系的临床表型、基因型和家系特征.方法 收集Kennedy病患者的临床资料,用基因分析的方法 ,明确患者及家族成员雄激素受体基因第1外显子CAG序列的重复数.结果 A家系4代共58人,先证者39岁隐袭起病.B家系5代共61人,有两例患者分别于39岁、41岁缓慢起病.3例患者均以下运动神经元损害为特征,都出现了雄激素不敏感综合征的相关表现.血清肌酶呈轻中度升高;肌电图呈广泛前角损害;肌肉活检示神经源性肌萎缩;雄激素受体基因第1外显子中CAG重复数分别为49、48、47.两个家系的遗传方式均为X连锁隐性遗传.结论 Kennedy病多为中年男性隐袭起病,主要表现为延髓肌和脊髓肌的萎缩和无力,基因分析有助于对本病的确诊,并可明确携带者,以进行遗传咨询及产前诊断.

Study on clinical manifestation, genotype and genetic characteristics of two Kennedy disease pedigrees

Objective To investigate the clinical manifestations, genotypes, and genetic characteristics of two pedigrees with Kennedy disease. Methods The clinical data of the patients from two Kennedy disease families were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. Results Family A was composed of 58 individuals in 4 generations. The proband had onset at 39 years old. There were two Kennedy disease patients in family B which included 61 individuals in 5 generations. The two patients had onset at 39 and 41 years old, respectively. All the three patients displayed limbs and bulbar muscular weakness because of the damage of lower motor neurons. They had androgen insensitivity syndrome in common, and showed mild or moderate increase in serum creatine kinase level. The electromyogram showed wild damage in anterior horn of spinal cord. Muscle biopsy displayed neurogenic muscular atrophy. The numbers of the CAG repeat expansion in the androgen receptor gene of the three patients were 49, 48, and 47, respectively. X-linked recessive mode of inheritance was demonstrated by pedigree analysis in the two families. Conclusion Kennedy disease usually occurs in mid-adulthood man. The clinical features are the weakness and wasting of limbs and bulbar muscles. Genetic analysis contributes to diagnosis and identification of carriers, and is beneficial to genetic counseling and prenatal diagnosis.