Yonsei Med J.  2015 Jul;56(4):993-997. 10.3349/ymj.2015.56.4.993.

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

• Song JS
• Kim KA
• Min JH
• Ki CS
• Kim JW
• Sung DH
• Kim BJ

• KMID: 2366340
• DOI: http://doi.org/10.3349/ymj.2015.56.4.993

Abstract

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.

Keyword

Androgen receptor gene; CAG repeats; genotype-phenotype correlation; spinal and bulbar muscular atrophy

MeSH Terms

Activities of Daily Living
Adult
Age of Onset
Asian Continental Ancestry Group/*genetics
Bulbo-Spinal Atrophy, X-Linked/genetics/*physiopathology
Disease Progression
Female
Genes, Recessive
Genetic Association Studies
Genotype
Humans
Male
Middle Aged
Muscle Weakness/*physiopathology
Muscular Atrophy, Spinal
Muscular Disorders, Atrophic/*genetics
Phenotype
Receptors, Androgen/*genetics
Republic of Korea
Trinucleotide Repeats/genetics
Receptors, Androgen

Figure

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  Fig. 1 Distribution of ADL scores at onset and at diagnosis. ADL, activities of daily living.

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  Fig. 2 Correlations of CAG-repeat number and the age at onset of any related symptoms and muscle weakness (A) and correlation of the age at onset and the rate of diseae progression (B). (A) There were significant correlations between CAG number and the age at onset of any related symptoms and at onsets of both muscle weakness. (B) There was marginal correlation between the age at onset and the rate of disease progression.

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