{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:53:26Z","timestamp":1790394806525,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,21]],"date-time":"2015-03-21T00:00:00Z","timestamp":1426896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103446"],"award-info":[{"award-number":["P20GM103446"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103464"],"award-info":[{"award-number":["P20GM103464"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012465","name":"Nemours Foundation","doi-asserted-by":"crossref","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}],"id":[{"id":"10.13039\/100012465","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Nemours Fund for Children's Health","award":["no applicable"],"award-info":[{"award-number":["no applicable"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Abstract<\/jats:title>Proximal spinal muscular atrophy (SMA<\/jats:styled-content>) is an early\u2010onset motor neuron disease characterized by loss of \u03b1<\/jats:italic>\u2010motor neurons and associated muscle atrophy. SMA<\/jats:styled-content> is caused by deletion or other disabling mutation of survival motor neuron 1<\/jats:italic> (SMN<\/jats:styled-content>1<\/jats:italic>). In the human genome, a large duplication of the SMN<\/jats:styled-content>\u2010containing region gives rise to a second copy of this gene (SMN<\/jats:styled-content>2<\/jats:italic>) that is distinguishable by a single nucleotide change in exon 7. Within the SMA<\/jats:styled-content> population, there is substantial variation in SMN<\/jats:styled-content>2<\/jats:italic> copy number; in general, those individuals with SMA<\/jats:styled-content> who have a high SMN<\/jats:styled-content>2<\/jats:italic> copy number have a milder disease. Because SMN<\/jats:styled-content>2<\/jats: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 SMN<\/jats:styled-content>1<\/jats:italic> and SMN<\/jats:styled-content>2<\/jats:italic> copy numbers in DNA<\/jats:styled-content> samples using an array\u2010based digital PCR<\/jats:styled-content> (dPCR<\/jats:styled-content>) system. This dPCR<\/jats:styled-content> assay can accurately and reliably measure the number of SMN<\/jats:styled-content>1<\/jats:italic> and SMN<\/jats:styled-content>2<\/jats:italic> copies in DNA<\/jats:styled-content> samples. In a cohort of SMA<\/jats:styled-content> patient\u2010derived cell lines, the assay confirmed a strong inverse correlation between SMN<\/jats:styled-content>2<\/jats:italic> copy number and disease severity. Array dPCR<\/jats:styled-content> is a practical technique to determine, accurately and reliably, SMN<\/jats:styled-content>1<\/jats:italic> and SMN<\/jats:styled-content>2<\/jats:italic> copy numbers from SMA<\/jats:styled-content> samples.<\/jats:p>","DOI":"10.1002\/mgg3.141","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T17:23:02Z","timestamp":1427217782000},"page":"248-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["SMN1<\/i> and SMN2<\/i> copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR"],"prefix":"10.1002","volume":"3","author":[{"given":"Deborah L.","family":"Stabley","sequence":"first","affiliation":[{"name":"Nemours Biomolecular Core Laboratory Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee W.","family":"Harris","sequence":"additional","affiliation":[{"name":"Center for Applied Clinical Genomics Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Nemours Biomolecular Core Laboratory Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Chubbs","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Delaware Newark Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Lozo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Delaware Newark Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins University Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn J.","family":"Swoboda","sequence":"additional","affiliation":[{"name":"Neurogenetics Research Program Center for Human Genetics Research Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky L.","family":"Funanage","sequence":"additional","affiliation":[{"name":"Center for Applied Clinical Genomics Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Center for Pediatric Research Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Department of Pediatrics Thomas Jefferson University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Applied Clinical Genomics Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Center for Pediatric Research Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Department of Pediatrics Thomas Jefferson University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Division of Orthopedics Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mena","family":"Scavina","sequence":"additional","affiliation":[{"name":"Division of Neurology Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Sol\u2010Church","sequence":"additional","affiliation":[{"name":"Nemours Biomolecular Core Laboratory Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-6400","authenticated-orcid":false,"given":"Matthew E. R.","family":"Butchbach","sequence":"additional","affiliation":[{"name":"Center for Applied Clinical Genomics Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Department of Biological Sciences University of Delaware Newark Delaware"},{"name":"Center for Pediatric Research Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington Delaware"},{"name":"Department of Pediatrics Thomas Jefferson University Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10221"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.1.97"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182017c05"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01262-08"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1205"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033572"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-0528.2002.02083.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.08.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.183038"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21350"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200009)16:3<253::AID-HUMU8>3.0.CO;2-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-007-0093-1"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.066969"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/71709"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803d35bc"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.373"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318271f7e4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.10"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.05.005"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-265"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.259"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6307"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2011.0149"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/515465"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.01.006"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1177"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.3.333"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12031"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/302160"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.15.6.409"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.08.002"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e318220d523"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30251"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000227970.60450.b2"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01200.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24114"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20160"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017067"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.134"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20473"},{"key":"e_1_2_7_45_1","first-page":"444","article-title":"Quantitation of targets for PCR by use of limiting dilution","volume":"13","author":"Sykes P. J.","year":"1992","journal-title":"Biotechniques"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.02.006"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90732-7"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21173"},{"key":"e_1_2_7_49_1","first-page":"28.3.1.","article-title":"Establishment and culture of human skin fibroblasts","volume":"28","author":"Villegas J.","year":"2005","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9236"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks203"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0156-7"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000172860.41953.12"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1lc20126c"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.141","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:29Z","timestamp":1696550429000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,21]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1002\/mgg3.141"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.141","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,21]]},"assertion":[{"value":"2015-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}