Srivistava et al. [2001] described a 5-year-old boy with delayed motor development, hypotonia, wasting, and weakness. The age of onset was approximately 9-10 months. Cognitive development was normal, and his muscle weakness was predominantly distal. He was born to non-consanguineous parents and there was no family history of similar disease. Tests to detect the presence or absence of the SMN1 gene, homozygous deletions of which are found in most patients with spinal muscular atrophy (SMA), were performed on DNA extracted from peripheral blood leukocytes of the patient, his unaffected parents and brother, and normal controls. These tests also detect the presence or absence of the SMN2 gene. SMN2, but not SMN1, was homozygously deleted in this patient. Sequencing of exon 7 of SMN1 did not reveal any small, non-deletion mutations.
To quantitate the number of SMN1 and SMN2 gene copies in the patient, his family, and normal controls, the authors amplified and separated SMN1 and SMN2 using the method of van der Steege et al. [1995]. This method uses 35 cycles of polymerase chain reaction (PCR) and was designed to detect homozygous deletions of SMN1 (and/or SMN2). Because the amplification of SMN1 and SMN2 starts to plateau at approximately 26 cycles of PCR [Chen et al., 1999], the method of van der Steege et al. is inappropriate for the quantitation of SMN1 or SMN2 copy number. Fewer cycles of PCR, as well as genomic and internal standards, are required [McAndrew et al., 1997;Chen et al., 1999].
The authors' conclusion that ''a deletion of SMN2 may also result in the SMA phenotype'' is misleading. Approximately 5% of normal, asymptomatic individuals lack both copies of SMN2 [Lefebvre et al., 1995]. Therefore, although the number of copies of SMN2 may affect the severity of SMA [Coovert et al., 1997;Lefebvre et al., 1997], homozygous deletion of SMN2, by itself, does not cause SMA.