| Objective In order to understand Kennedy disease better,the clinical manifestations, genotypes,and genetic characteristics of Kennedy disease from 2 pedigrees were investigated. Method The clinical datas of patients from 2 Kennedy disease families were collected. Extracting DNA from leukocytes ofâ…¢9 of A family existing in peripheral blood,the CAG repeat fragment in exon 1 of the gene encoding the androgen receptor was amplified by PCR. Following the sequencing PCR,sequencing was perfomed,then we can count the number of CAG.The number of CAG was deduced according to DNA ofâ…¢9 from family A by means of fragment analysis.According to the clinical history and objective examinations,we began to investigate families,clinical data were collected and genetic analysis were performed in similar method.The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis.Result The result of clinical data Family A was composed of 58 individuals in 4 generations,and the proband onset at 39-year old.There are 2 Kennedy disease patients(â…¢12 &â…¢8) in family B which was composed of 61 individuals in 5 generations.The two patients onset at 39-year old and 41-year old,respectively.All the three patients displayed limb and bulbar muscular weakness because of the damage of lower motor neuron.Androgen insensitivity syndrome was common in Kennedy disease patients.All the symptoms characterized by the slowly progressive course, which became more and more serious.Muscular cramp in bothâ…¢12 andâ…¢8 of family B has been lasting for 20 years and 19 years,respectively.Physical examination showed proximal limbs muscular atrophy to different extent.Pharyngeal reflex(+).All the three patients showed mild and moderate increase in serum creatin kinase level,mild increase in serum glutamic pyruvict ransaminase and glutamic-oxalacetic transaminase.â…¢12 andâ…¢8 of family B showed increase in triglyceride,besides this,â…¢8 of family B showed increase in total cholesterol and low density iipoprotein cholesterol as well.Bothâ…¢12 andâ…¢8 of family B were confirmed fatty liver by abdominal B-ultrasound.The electromyogram showed wild damage of anterior horn of spinal cord.The results suggested that neurogenic damage after making pathological analysis of right gastrocnemius muscle,left quadriceps femoris muscle and left deltoid from patientâ…¢12 of family B.The result of Sex hormone were normal in the 3 patients.2 The result of gene analysis 40 people accepted gene analysis in the 2 families,of the all,there were 17(1 in family A and 16 in family B) males and 23 females.3 patients were detected(family A:â…¢9;family B:â…¢12 &â…¢8),the number of trinucleotide CAG repeat expansion in exon 1 of the gene encoding the androgen receptor is 49,48,and 47,respectively.Besides this,10 carriers were detected(family A:â…¡1,â…¡4,â…¢13 andâ…£7;family B:â…¡1,â…¢3,â…¢10,â…£7,â…£16 andâ…¤2).3 The result of pedigree analysis The 2 families have some characteristics according to pedigree analysis,including it still have patients in the 2 families even if their parents are normal;virulence gene can be transmitted by both patients and carriers;all the carriers has no symptoms;virulence gene of patients from their mothers can transmite to their daughters,but can not to their son,criss-cross inheritance can be found.Conclusion Kennedy disease usually occurs in middle-aged males and onsets insidiously,whose major symptoms not only include medulla oblongata and spinal muscular atrophy and muscle weakness,but also have some symptoms related to incomplete androgen-insensitivity syndrome.Electromyography show neurogenic change,serum creatase show mild to moderate increase.Kennedy disease is not only a X-linked recessive inherited disease which is associated with dynamic mutation.It is caused by a trinucleotide CAG repeat expansion in exon 1 of the gene encoding the androgen receptor.The number of the CAG repeat is polymorphic and steady in the normal people,but unsteady in the patients.There is some relationship between the number of trinucleotide CAG repeat expansion in exon 1 of the gene encoding the androgen receptor and pathogenetic condition,age at onset becomes more and more earlier and symptoms become more and more serious as the number of trinucleotide CAG is more and more greater.There is no specific treatment for the disease.Gene analysis can contribute to identify patients and carriers,the most effective methods to prevent the patients with Kennedy disease from being born include genetic consultancy,guidence to marrying and fostering and prenatal diagnosis. |
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