{"id":186,"date":"2023-11-27T00:00:00","date_gmt":"2023-11-27T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1266353"},"modified":"2023-11-27T00:00:00","modified_gmt":"2023-11-27T00:00:00","slug":"molecular-characterization-of-novel-and-rare-dna-variants-in-patients-with-galactosemia","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/11\/27\/molecular-characterization-of-novel-and-rare-dna-variants-in-patients-with-galactosemia\/","title":{"rendered":"Molecular characterization of novel and rare DNA variants in patients with galactosemia"},"content":{"rendered":"<p><bold>Introduction:<\/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.<\/p><p><bold>Methods:<\/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 <italic>GALT<\/italic>, <italic>GALK1<\/italic>, and <italic>GALE<\/italic> genes.<\/p><p><bold>Results:<\/bold> Our approach led to the identification of eight rare nonsynonymous DNA variants. Four of these variants, namely, p.Arg204Gln and p.Met298Ile in <italic>GALT<\/italic>, p.Arg68Leu in <italic>GALK1<\/italic>, and p.Ala180Thr in <italic>GALE<\/italic>, were already recorded in relevant databases, yet their clinical significance is uncertain. The other four variants, namely, p.Phe245Leu in <italic>GALT<\/italic>, p.Gly193Glu in <italic>GALK1<\/italic>, and p.Ile266Leu and p.Ala216Thr in the <italic>GALE<\/italic> gene, were novel. <italic>In silico<\/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.<\/p><p><bold>Discussion:<\/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.<\/p>","protected":false},"excerpt":{"rendered":"<p>Introduction: 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\/la&#8230;<\/p>\n","protected":false},"author":44,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,12,13],"tags":[],"class_list":["post-186","post","type-post","status-publish","format-standard","hentry","category-articulos","category-enfermedades-raras","category-frontiers-in-genetics"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/186","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/44"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=186"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/186\/revisions"}],"predecessor-version":[{"id":187,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/186\/revisions\/187"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=186"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=186"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=186"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}