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NGS revealed a homozygous <jats:italic>RFT1<\/jats:italic> (c.16G\u2009&gt;\u2009T p.Val6Leu) variant of unknown significance that is predicted to be benign. Metabolic radiolabelling of the patient\u2019s fibroblasts did not reveal the accumulation of truncated Man<jats:sub>5<\/jats:sub>Glc<jats:italic>N<\/jats:italic>Ac<jats:sub>2<\/jats:sub>-PP-dolichol expected of RFT1-CDG but rather an accumulation of Man<jats:sub>7<\/jats:sub>Glc<jats:italic>N<\/jats:italic>Ac<jats:sub>2<\/jats:sub>-PP-dolichol, characteristic of ALG12-CDG. Revaluation of the NGS data revealed a homozygous (22_50311909A_G, c.-79\u2009+\u20092\u00a0T\u2009&gt;\u2009C) variant that modifies the second nucleotide of the first intron of the <jats:italic>ALG12<\/jats:italic> gene upstream of the first coding exon (exon 2). Sequencing of <jats:italic>ALG12<\/jats:italic> cDNA revealed a 4-base insertion between exon 1 and exon 2 suggesting a shift in mRNA splicing in this intron to a putative new GU donor site. The patient\u2019s fibroblasts display 3% of control <jats:italic>ALG12<\/jats:italic> mRNA levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This is the first description of a pathogenic intronic <jats:italic>ALG12<\/jats:italic> variant upstream of the first coding exon. The modification of the splicing process between intron 1 and exon 2, the very low transcript level and the absence of other mutations in the patient's ALG12 gene lead us to conclude that this <jats:italic>ALG12<\/jats:italic> variant is a predicted Loss of Function (pLOF) variant.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03535-4","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T15:30:53Z","timestamp":1740151853000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An ALG12-CDG patient with a novel homozygous intronic mutation associated with low ALG12 mRNA"],"prefix":"10.1186","volume":"20","author":[{"given":"Sandrine","family":"Vuillaumier-Barrot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Dupr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Andriantsihoarana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Desportes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cheillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart E. 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For gene studies, signed informed consent protocols were obtained from the parents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"SV, TD, TA, VD, DC, SM, IC: Final approval of the version to be published.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"81"}}