Research of serum myoglobin detection in patients with Kennedy's Disease / 临床神经病学杂志

Objective To explore the significance of serum myoglobin detection in the diagnosis and evaluation of Kennedy`s disease (KD).Methods The level of serum myoglobin (Myo) was detected in 60 KD patients and 30 amyotrophic lateral sclerosis (ALS) patients.Results The serum Myo level and abnormal rate in KD group were significantly higher than those in ALS group (all P0.05).There was no overlap of serum Myo level between the two groups.There was no significant difference of serum Myo level and CAG repeated number of ALS (r=-0.193,P>0.05).Conclusion Myo is likely as an easy and sensitive biomarker, used to identify the KD and special type of ALS, and used in the evaluation of the KD condition in the future.

Clinical Characteristics and Genotype-Phenotype Correlation of Korean Patients with Spinal and Bulbar Muscular Atrophy

PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease characterized by proximal muscle weakness, muscle atrophy, and fasciculation. Although SBMA is not uncommon in Korea, there is only one study reporting clinical characteristics and genotype-phenotype correlation in Korean patients. MATERIALS AND METHODS: In this study, age at the onset of symptoms, the score of severity assessed by impairment of activities of daily living milestones, and rate of disease progression, and their correlations with the number of CAG repeats in the androgen receptor (AR) gene, as well as possible correlations among clinical characteristics, were analyzed in 40 SBMA patients. RESULTS: The median ages at onset and at diagnosis were 44.5 and 52.5 years, respectively, and median interval between onset and diagnosis and median rate of disease progression were 5.0 years and 0.23 score/year, respectively. The median number of CAG repeats in the AR gene was 44 and the number of CAG repeats showed a significant inverse correlation with the age at onset of symptoms (r=-0.407, p=0.009). In addition, patients with early symptom onset had slower rate of disease progression. CONCLUSION: As a report with the largest and recent Korean cohort, this study demonstrates clinical features of Korean patients with SBMA and reaffirms the inverse correlation between the age at disease onset and the number of CAG repeats. Interestingly, this study shows a possibility that the rate of disease progression may be influenced by the age at onset of symptoms.

Tremor in X-linked recessive spinal and bulbar muscular atrophy (Kennedy's disease)

OBJECTIVE: To study tremor in patients with X-linked recessive spinobulbar muscular atrophy or Kennedy's disease. METHODS: Ten patients (from 7 families) with a genetic diagnosis of Kennedy's disease were screened for the presence of tremor using a standardized clinical protocol and followed up at a neurology outpatient clinic. All index patients were genotyped and showed an expanded allele in the androgen receptor gene. RESULTS: Mean patient age was 37.6 years and mean number of CAG repeats 47 (44-53). Tremor was present in 8 (80 percent) patients and was predominantly postural hand tremor. Alcohol responsiveness was detected in 7 (88 percent) patients with tremor, who all responded well to treatment with a β-blocker (propranolol). CONCLUSION: Tremor is a common feature in patients with Kennedy's disease and has characteristics similar to those of essential tremor.

A clinical, pathological and genetic study of a Chinese family with Kennedy disease / 第二军医大学学报

Objective: To report a genetically proven Kennedy disease pedigree in China and to discuss its clinical presentations, pathological features and molecular mechanism, so as to provide more information on Kennedy disease. Methods: We conducted a complete survey of the family, including 3 generations and 41 individuals. The proband was given a thorough clinical examination including CK level, EMG, testosterone level, nerve biopsy, and muscle biopsy. Genomic DNA was extracted from the peripheral blood; the repeats of CAG in the exon 1 of androgen receptor was amplified by PCR and sequenced directly. Results: The sequencing result showed that the proband(III-11) had a CAG repeat of 54); one patient (IV-2) had a CAG repeat of 55; one had a CAG repeat of 54; one presymptomatic individual had a CAG repeat of 54(IV-8). There were 3 female carriers (II-6, III-3, and III-15). The CPK and testosterone levels were increased in the proband. EMG revealed neurogenic injury. Nerve biopsy revealed demylination change in the peripheral nerve and muscle biopsy revealed muscle atrophy originated from nerve. Conclusion: Kennedy has no characteristic clinical symptoms, and gene diagnosis is the gold standard. The progression of SBMA is usually much slower compared with those of bulbar atrophy and atrophic lateral sclerosis(ALS).

Trinucleotide Repeat Polymorphisms of Spinal and Bulbar Muscular Atrophy (SBMA) Gene in Asian Populations / 체질인류학회지

I previously reported the PCR-based Spinal and bulbar muscular atrophy (SBMA) region polymorphisms in the three northeast Asian populations (Chinese, Koreans, Japanese) and Caucasians. Here I update this analysis by including the data of the allele distribution in 378 unrelated individuals from four populations in Asia. In this study I investigated PCR-based CAG repeat polymorphism on the SBMA locus among four Asian populations (Mongolian, Evenki, Orochon, Negrito) and performed the statistical analysis on the eight populations including the previously analyzed data. Both statistical analyses of one-way ANOVA (F=3.284, P=0.002) and Kruskal-Wallis test (chi-square=21.542, DF=7, P=0.003) showed remarkable differences in CAG allele distributions among the populations. Post-hoc test showed that the difference between Negritos and Caucasians was especially significant (Scheffe: P=0.042; Bonferroni: P=0.004). Also a significant differences among Northeast Asians, Caucasians and Negritos (Southeast Asian) were detected by these two tests (ANOVA; F=8.132, P.0.000, Kruskal-Wallis; chi-square=16.614, DF=2, P.0.000). Post-hoc test showed that the differences between Negritos and Caucasias was also especially significant (Scheffe: P=0.001; Bonferroni: P=0.000) among these three groups. These data present that the CAG repeat polymorphism of SBMA gene has a useful information for studies of human population genetics.