SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. Issue 4 (21st March 2015)

• Record Type: Journal Article
• Authors: Stabley, Deborah L.; Harris, Ashlee W.; Holbrook, Jennifer; Chubbs, Nicholas J.; Lozo, Kevin W.; Crawford, Thomas O.; Swoboda, Kathryn J.; Funanage, Vicky L.; Wang, Wenlan; Mackenzie, William; Scavina, Mena; Sol‐Church, Katia; Butchbach, Matthew E. R.
• Is Part Of: Molecular genetics & genomic medicine. Volume 3:Issue 4(2015:Jul.)
• Page Start: 248
• Page End: 257
• Publication Date: 2015-03-21
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.141
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg3141-abs-0001"> <title>Abstract</title> <p>Proximal spinal muscular atrophy (SMA) is an early‐onset motor neuron disease characterized by loss of <italic>α</italic>‐motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutation of <italic>survival motor neuron 1</italic> (<italic>SMN1</italic>). In the human genome, a large duplication of the SMN‐containing region gives rise to a second copy of this gene (<italic>SMN2</italic>) that is distinguishable by a single nucleotide change in exon 7. Within the SMA population, there is substantial variation in <italic>SMN2</italic> copy number; in general, those individuals with SMA who have a high <italic>SMN2</italic> copy number have a milder disease. Because <italic>SMN2</italic> functions as a disease modifier, its accurate copy number determination may have clinical relevance. In this study, we describe the development of an assay to assess <italic>SMN1</italic> and <italic>SMN2</italic> copy numbers in DNA samples using an array‐based digital PCR (dPCR) system. This dPCR assay can accurately and reliably measure the number of <italic>SMN1</italic> and <italic>SMN2</italic> copies in DNA samples. In a cohort of SMA patient‐derived cell lines, the assay confirmed a strong inverse correlation between <italic>SMN2</italic> copy number and disease severity. Array dPCR is a practical technique to determine, accurately and reliably, <italic>SMN1</italic> and <italic>SMN2</italic> copy numbers from SMA samples.</p> </abstract>