UMMS Affiliation

New England Newborn Screening Program; Division of Genetics, Department of Pediatrics

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Document Type



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Medical Genetics | Pediatrics


Promising treatments for spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, prompted calls for inclusion in newborn screening (NBS). In January 2018, the New England Newborn Screening Program (NENSP) began statewide screening for SMA using a tiered algorithm looking for the absence of SMN1 Exon 7. When results from the first and second tier needed reconciliation, we developed and validated a third tier DNA sequencing assay to ensure the presence or absence of SMN1 Exon 7. All nine infants referred to specialty centers through NBS showed single base substitution of c.840C > T, and were confirmed to have SMA. Further, a minor sequencing protocol modification allowed the estimation of SMN2 copy number in SMA affected patients; we developed and validated a copy-number assay yielding 100% match with seven previously characterized specimens of SMA patients. All nine SMA-affected infants found through NBS were also assayed for SMN2 copy number. Results were comparable but not 100% matched with those that were reported by independent diagnostic laboratories. In conclusion, a sequencing protocol confirms NBS findings from real-time qPCR, and its modified application allows NBS programs that have sequencing capabilities to provide SMN2 copy numbers without the need for additional instrumentation.


SMA, SMN2, copy number, newborn screening, sequencing

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Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

DOI of Published Version



Kumar B, Barton S, Kordowska J, Eaton RB, Counihan AM, Hale JE, Comeau AM. Novel Modification of a Confirmatory SMA Sequencing Assay that Can Be Used to Determine SMN2 Copy Number. Int J Neonatal Screen. 2021 Jul 21;7(3):47. doi: 10.3390/ijns7030047. PMID: 34449530; PMCID: PMC8395917. Link to article on publisher's site

Journal/Book/Conference Title

International journal of neonatal screening

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Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.