Investigation of carrier frequency for spinal muscular atrophy in Thailand using dried blood spot specimens

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder, characterized by the degeneration of motor neurons of the spinal cord, thus leading to the deaths of newborns. More than 95% of SMA patients are caused by the absence of survival motor neuron 1 (SMN1) gene exon 7, located on chromosome 5q13. The SMA disease prevalence and SMA mutations in Thailand have never been reported. In this study, we aimed to explore the frequency of SMA carriers (heterozygous, loss of exon 7 in SMN1 gene) and simultaneously determine the SMN2-exon 7 copy number in Thai neonate population. We used a denaturing high-performance liquid chromatography (DHPLC)-based semiquantitative multiplex-PCR technique to detect the copy number of SMN genes by comparing with two reference genes, palmitoyl-protein thioesterase 1 and proteolipid protein 1. DNA samples were extracted from dried blood spot (DBS) specimens (n = 1,000) leftover from the Thai National Neonatal Screening Program. Results indicated that the SMA carrier frequency in the Thai newborns was 2.8% (1/36 cases). According to this data, the prevalence of SMA caused by homozygous deletion of SMN1 exon 7 in Thai newborns was estimated at 1 in 5,102 cases. In conclusion, we reported a relatively high rate of SMA carriers in Thai newborns. Additionally, the estimated incidence of SMA found in this study was comparable to that reported in other countries. Therefore, SMA could be considered as a national health problem and results from this study may be useful to establish a national program for clinical, prenatal diagnosis and genetic counseling to effectively prevent SMA in Thailand.