Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay
Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the <i>SMN1</i> gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been developed and ado...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/7/4/69 |
| _version_ | 1797503630797963264 |
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| author | Stuart P. Adams Emma Gravett Natalie Kent Susanne Kricke Adeboye Ifederu Mariacristina Scoto Salma Samsuddin Francesco Muntoni |
| author_facet | Stuart P. Adams Emma Gravett Natalie Kent Susanne Kricke Adeboye Ifederu Mariacristina Scoto Salma Samsuddin Francesco Muntoni |
| author_sort | Stuart P. Adams |
| collection | DOAJ |
| description | Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the <i>SMN1</i> gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been developed and adopted for use in many countries, including the UK. Success of these treatments depends on early diagnosis and intervention in newborn babies, and many countries have implemented a newborn screening (NBS) or pilot NBS program to detect <i>SMN1</i> exon 7 deletions on dried blood spots. In the UK, there is no current NBS program for SMA, and no pilot studies have commenced. For consideration of adoption of NBS for a new condition, numerous criteria must be satisfied, including critical assessment of a working methodology. This study uses a commercially available real-time PCR assay to simultaneously detect two different DNA segments (<i>SMN1</i> exon 7 and control gene <i>RPP30</i>) using DNA extracted from a dried blood spot. This study was carried out in a routine clinical laboratory to determine the specificity, sensitivity, and feasibility of SMA screening in a UK NBS lab setting. Just under 5000 normal DBSs were used alongside 43 known SMA positive DBSs. Study results demonstrate that NBS for SMA using real-time PCR is feasible within the current UK NBS Laboratory infrastructure using the proposed algorithm. |
| first_indexed | 2024-03-10T03:54:25Z |
| format | Article |
| id | doaj.art-341a1c50d97b4741acc7c5fa038ac37b |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-10T03:54:25Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-341a1c50d97b4741acc7c5fa038ac37b2023-11-23T08:50:04ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2021-10-01746910.3390/ijns7040069Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening AssayStuart P. Adams0Emma Gravett1Natalie Kent2Susanne Kricke3Adeboye Ifederu4Mariacristina Scoto5Salma Samsuddin6Francesco Muntoni7SIHMDS-Haematology, Camelia Botnar Labs, Great Ormond Street Hospital for Children, London WC1N 3JH, UKSIHMDS-Haematology, Camelia Botnar Labs, Great Ormond Street Hospital for Children, London WC1N 3JH, UKSIHMDS-Haematology, Camelia Botnar Labs, Great Ormond Street Hospital for Children, London WC1N 3JH, UKSIHMDS-Haematology, Camelia Botnar Labs, Great Ormond Street Hospital for Children, London WC1N 3JH, UKNewborn Screening Unit, Camelia Botnar Labs, Great Ormond Street Hospital for Children, London WC1N 3JH, UKDevelopmental Neurosciences Research & Teaching Department, Molecular Neurosciences, Dubowitz Neuromuscular Unit, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UKDevelopmental Neurosciences Research & Teaching Department, Molecular Neurosciences, Dubowitz Neuromuscular Unit, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UKDevelopmental Neurosciences Research & Teaching Department, Molecular Neurosciences, Dubowitz Neuromuscular Unit, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UKSpinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the <i>SMN1</i> gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been developed and adopted for use in many countries, including the UK. Success of these treatments depends on early diagnosis and intervention in newborn babies, and many countries have implemented a newborn screening (NBS) or pilot NBS program to detect <i>SMN1</i> exon 7 deletions on dried blood spots. In the UK, there is no current NBS program for SMA, and no pilot studies have commenced. For consideration of adoption of NBS for a new condition, numerous criteria must be satisfied, including critical assessment of a working methodology. This study uses a commercially available real-time PCR assay to simultaneously detect two different DNA segments (<i>SMN1</i> exon 7 and control gene <i>RPP30</i>) using DNA extracted from a dried blood spot. This study was carried out in a routine clinical laboratory to determine the specificity, sensitivity, and feasibility of SMA screening in a UK NBS lab setting. Just under 5000 normal DBSs were used alongside 43 known SMA positive DBSs. Study results demonstrate that NBS for SMA using real-time PCR is feasible within the current UK NBS Laboratory infrastructure using the proposed algorithm.https://www.mdpi.com/2409-515X/7/4/69spinal muscular atrophySMA<i>SMN1</i>newborn screeningNBSdried blood spot |
| spellingShingle | Stuart P. Adams Emma Gravett Natalie Kent Susanne Kricke Adeboye Ifederu Mariacristina Scoto Salma Samsuddin Francesco Muntoni Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay International Journal of Neonatal Screening spinal muscular atrophy SMA <i>SMN1</i> newborn screening NBS dried blood spot |
| title | Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay |
| title_full | Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay |
| title_fullStr | Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay |
| title_full_unstemmed | Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay |
| title_short | Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay |
| title_sort | screening of neonatal uk dried blood spots using a duplex smn1 screening assay |
| topic | spinal muscular atrophy SMA <i>SMN1</i> newborn screening NBS dried blood spot |
| url | https://www.mdpi.com/2409-515X/7/4/69 |
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