{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:25Z","timestamp":1787026825127,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Introduction<\/jats:title>\n \n Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by pathogenic variants in the\n SMN1<\/jats:italic>\n gene. The majority of SMA patients harbor a homozygous deletion of\n SMN1<\/jats:italic>\n exon 7 (95%). Heterozygosity for a conventional variant and a deletion is rare (5%) and not easily detected, due to the highly homologous\n SMN2<\/jats:italic>\n gene interference.\n SMN2<\/jats:italic>\n mainly produces a truncated non-functional protein (SMN-d7) instead of the full-length functional (SMN-FL). We hereby report a novel\n SMN1<\/jats:italic>\n splicing variant in an infant with severe SMA.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n MLPA was used for\n SMN1\/2<\/jats:italic>\n exon dosage determination. Sanger sequencing approaches and long-range PCR were employed to search for an\n SMN1<\/jats:italic>\n variant. Conventional and improved Real-time PCR assays were developed for the qualitative and quantitative\n SMN1\/2<\/jats:italic>\n RNA analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The novel\n SMN1<\/jats:italic>\n splice-site variant c.835-8_835-5delinsG, was identified in compound heterozygosity with\n SMN1<\/jats:italic>\n exons 7\/8 deletion. RNA studies revealed complete absence of\n SMN1<\/jats:italic>\n exon 7, thus confirming a disruptive effect of the variant on\n SMN1<\/jats:italic>\n splicing. No expression of the functional\n SMN1<\/jats:italic>\n -FL transcript, remarkable expression of the\n SMN1-<\/jats:italic>\n d7 and increased levels of the\n SMN2<\/jats:italic>\n -FL\/\n SMN2<\/jats:italic>\n -d7 transcripts were observed.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n We verified the occurrence of a non-deletion\n SMN1<\/jats:italic>\n variant and supported its pathogenicity, thus expanding the\n SMN1<\/jats:italic>\n variants spectrum. We discuss the updated SMA genetic findings in the Cypriot population, highlighting an increased percentage of intragenic variants compared to other populations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2023.1241195","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T05:02:05Z","timestamp":1695272525000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Spinal muscular atrophy type I associated with a novel SMN1 splicing variant that disrupts the expression of the functional transcript"],"prefix":"10.3389","volume":"14","author":[{"given":"Christina","family":"Votsi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelitsa","family":"Koutsou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Ververis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthi","family":"Georghiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paschalis","family":"Nicolaou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tanteles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyproula","family":"Christodoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7S9","DOI":"10.1016\/S0929-693X(20)30270-0","article-title":"Molecular 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