Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused by mutations of the survival of motor neuron 1 (SMN1) gene. Approximately 90-95% of SMA patients have a homozygous deletion of SMN1, and 5-10% of patients are believed to have subtle mutations. The molecular diagnosis of SMN1 subtle mutations is hampered by a highly homologous SMN2 gene. It is important to establish a rational molecular diagnostic procedure for SMN1 subtle mutations. We analyzed the SMN1 mutations in nine nonhomozygous patients by the following procedures: multiplex ligation-dependent probe amplification, genomic sequencing, T-A cloning on cDNA or genomic level, and/or real-time quantitative analysis. By the above molecular diagnostic procedure, six SMN1 subtle mutations, including c.5C>G(p.Ala2Gly), c.22_23 insA (p.Ser8LysfsX23), c.40G>T(p.Glu14X), c.43C>T(p.Gln15X), c.683T>A(p.Leu228X), and c.56delT(p.Val19GlyfsX21), were identified in nine Chinese patients. p.Glu14X has not been reported previously. Compared with the level of full-length SMN1 transcripts in the healthy carriers (14.1±4.5), the patient with p.Ala2Gly had no significant reduction (13.9±3.64, p=0.955). However, the levels in the patients carrying other mutations were significantly reduced (0.27±0.139 to 13.9±3.64, p=0.000-0.004). We present a reliable and rational diagnostic procedure for SMN1 subtle mutations, which would be helpful in molecular diagnosis of SMA compound heterozygotes. Our work extends the SMN1 mutation spectrum.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.