DECREASED EXPRESSION OF FULL-LENGTH MESSENGER-RNA FOR (C)BCD541 DOES NOT CORRELATE WITH SPINAL MUSCULAR-ATROPHY PHENOTYPE SEVERITY

Spinal muscular atrophy (SMA) is characterized by degeneration of spin al cord anterior horn cells and muscular atrophy and has three phenoty pes based on clinical severity and age of onset. One of the responsibl e genes for SMA is the survival motor neuron (SMN) gene, which is homo zygously absent or interrupted in more than 90% of SMA patients. The ( c)BCD541 (BCD) gene is a highly homologous copy of the SMN gene, which has a single synonymous transition in the coding region and may compe nsate for the loss of the SMN gene. To evaluate the effects of the BCD gene expression on the phenotypes of SMA, we examined lymphocyte mRNA from 9 SMA patients lacking the SMN gene, 10 asymptomatic parents, an d 15 control subjects. We amplified mRNA fragments containing exon 7 o f the SMN or BCD genes using reverse transcription-polymerase chain re action since the transcript lacking exon 7 encodes a putative protein with a different C-terminal end. We used glyceraldehyde-3-phosphate de hydrogenase (GAPDH) transcript as an internal control, and the relativ e expression level of the SMN or BCD gene was shown as the ratio of SM N or BCD transcript to GAPDH transcript (S/G ratio). The mean S/G rati os of the patients were significantly lower than that of the parents a nd controls. However, among the patients examined in this study, there was no relationship between the S/G ratios and phenotypes of SMA. The results showed that the BCD gene expression was not related to the ph enotypes of SMA. Furthermore, there was an overlap between the S/G rat ios in patients and controls. As our discrimination study showed that the S/G ratio reflected the expression of the BCD transcripts in patie nts and the SMN transcripts in controls, this finding suggested that t he BCD gene expression per se does not compensate for the loss of the SMN gene.