{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T03:51:42Z","timestamp":1781063502126,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["2556"],"award-info":[{"award-number":["2556"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003448","name":"General Secretariat for Research and Technology","doi-asserted-by":"publisher","award":["2556"],"award-info":[{"award-number":["2556"]}],"id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"Introduction:<\/jats:bold> Galactosemia is an inherited disorder caused by mutations in the three genes that encode enzymes implicated in galactose catabolism. Currently, the only available treatment for galactosemia is life-long dietary restriction of galactose\/lactose, and despite treatment, it might result in long-term complications.<\/jats:p>Methods:<\/jats:bold> Here, we present five cases of newborn patients with elevated galactose levels, identified in the context of the newborn screening program. Genetic analysis concerned a next generation sequencing (NGS) methodology covering the exons and adjacent splice regions of the GALT<\/jats:italic>, GALK1<\/jats:italic>, and GALE<\/jats:italic> genes.<\/jats:p>Results:<\/jats:bold> Our approach led to the identification of eight rare nonsynonymous DNA variants. Four of these variants, namely, p.Arg204Gln and p.Met298Ile in GALT<\/jats:italic>, p.Arg68Leu in GALK1<\/jats:italic>, and p.Ala180Thr in GALE<\/jats:italic>, were already recorded in relevant databases, yet their clinical significance is uncertain. The other four variants, namely, p.Phe245Leu in GALT<\/jats:italic>, p.Gly193Glu in GALK1<\/jats:italic>, and p.Ile266Leu and p.Ala216Thr in the GALE<\/jats:italic> gene, were novel. In silico<\/jats:italic> analysis of the possible effect of these variants in terms of protein function and stability was performed using a series of bioinformatics tools, followed by visualization of the substituted amino acids within the protein molecule. The analysis revealed a deleterious and\/or destabilizing effect for all the variants, supported by multiple tools in each case.<\/jats:p>Discussion:<\/jats:bold> These results, given the extreme rarity of the variants and the specific phenotype of the respective cases, support a pathogenic effect for each individual variant. Altogether, our study shows that targeted NGS methodologies may offer a time- and cost-effective approach for the genetic investigation of galactosemia and can assist in elucidating the complex genetic background of this disorder.<\/jats:p>","DOI":"10.3389\/fgene.2023.1266353","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T08:54:57Z","timestamp":1701075297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular characterization of novel and rare DNA variants in patients with galactosemia"],"prefix":"10.3389","volume":"14","author":[{"given":"Vasileios","family":"Maroulis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Agathangelidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Skouma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triantafyllia","family":"Sdogou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoussos N.","family":"Papadakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Papakonstantinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Girginoudis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos E.","family":"Vorgias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Aleporou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagoula","family":"Kollia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. 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