{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T23:27:19Z","timestamp":1783466839333,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["APP1194940"],"award-info":[{"award-number":["APP1194940"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA. Method: A retrospective cohort study was undertaken at Sydney Children\u2019s Hospital Network, the major SMA referral centre for New South Wales, Australia. Participants included children with genetically confirmed SMA born between 2005 and 2021. Data was collected on parent genotype inclusive of copy number of SMN1 exons 7 and 8. The number of SMN2 exon 7 copies were recorded for the affected children. Descriptive statistics were used to determine the proportion of carriers of 2+0 genotype classified as silent carriers. Chi-square test was used to correlate the association between parents with a heterozygous SMN1 exon 7 deletion and two copies of exon 8 and \u22653 SMN2 copy number in the proband. Results: SMA carrier testing was performed in 118\/154 (76.6%) parents, incorporating 59 probands with homozygous SMN1 deletions and one proband with compound heterozygote pathogenic variants. Among parents with a child with SMA, 7.6% had two copies of SMN1 exon 7. When only probands with a homozygous SMN1 exon 7 deletion were included, 6.9% of parents had two copies of SMN1 exon 7. An association was observed between heterozygous deletion of SMN1 exon 7 with two copies of exon 8 in a parent and \u22653 SMN2 copy number in the affected proband (p = 0.07). Conclusions: This study confirmed a small but substantial proportion of silent carriers not identified by conventional screening within an Australian context. Accordingly, the effectiveness of carrier screening for SMA is linked with genetic counselling to enable health literacy regarding high and low risk results and is complemented by new-born screening and maintaining clinical awareness for SMA. Gene conversion events may underpin the associations between parent carrier status and proband SMN2 copy number.<\/jats:p>","DOI":"10.3390\/genes14071403","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:34:30Z","timestamp":1688603670000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Carrier Frequency of Two SMN1 Genes in Parents of Symptomatic Children with SMA and the Significance of SMN1 Exon 8 in Carriers"],"prefix":"10.3390","volume":"14","author":[{"given":"Joanne E","family":"Davidson","sequence":"first","affiliation":[{"name":"Department of Neurology, Sydney Children\u2019s Hospitals Network, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline S","family":"Russell","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children\u2019s Hospital, Randwick, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelia Nunez","family":"Martinez","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children\u2019s Hospital, Randwick, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Mowat","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children\u2019s Hospital, Randwick, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi J","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, The Children\u2019s Hospital at Westmead, and Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin P","family":"Kirk","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children\u2019s Hospital, Randwick, Sydney, NSW 2031, Australia"},{"name":"Discipline of Paediatrics and Child Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didu","family":"Kariyawasam","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sydney Children\u2019s Hospitals Network, Sydney, NSW 2031, Australia"},{"name":"Discipline of Paediatrics and Child Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0902","authenticated-orcid":false,"given":"Michelle","family":"Farrar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sydney Children\u2019s Hospitals Network, Sydney, NSW 2031, Australia"},{"name":"Discipline of Paediatrics and Child Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene","family":"D\u2019Silva","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sydney Children\u2019s Hospitals Network, Sydney, NSW 2031, Australia"},{"name":"Discipline of Paediatrics and Child Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1750-1172-6-71","article-title":"Spinal muscular atrophy","volume":"6","author":"Mercuri","year":"2011","journal-title":"Orphanet J. 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