SMN2 유전자 복제수가 척수성 근위축 환자의 표현형에 미치는 영향에 대한 연구

초록

Purpose: Spinal muscular atrophy (SMA) is degenerative disease of motor neuroncaused by loss of survival motor neuron (SMN)1 gene. SMN2 gene is highly homologous to SMN1 and is known to influence disease severity according to its copy number. Our purpose was to investigate genotype-phenotype correlation between theSMN2 copy number and the clinical course in spinal muscular atrophy patients.Methods: The correlation between SMN2 copy number and clinical severity (subtype, ventilator support, mortality and independent walking) was analyzed.Results: The SMN2 copy number was analyzed in 60 SMA patients (male 29, female31). The average follow-up duration was 4.0 years (0.2 to 16.7). One patient had 1SMN2 copy and was on ventilator support. In 20 patients who had 2 SMN2 copies,19 (95.0%) were type I and 11 (55.0%) were on ventilator support. There were 4 mortalities in these patients. In 37 patients who had 3 SMN2 copies, 36 (97.3%) weretype II. The 3 patients (8.1%) were on ventilator support and 17 (45.9%) could walkindependently. The two patients had 4 SMN2 copies, each patient was type I and III.Two SMN2 copies were significantly correlated with earlier ventilator dependenceand higher mortality than three SMN2 copies.Conclusion: This is the first report that compared the relationship between SMN2 copy number and clinical phenotype in Korean SMA patients. The lower SMN2 genecopies were significantly correlated with severe clinical outcomes of SMA. However,additional biomarkers capable of predicting more detailed clinical outcomes withinsubtypes need to be further determined in an extended cohort.

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