{"id":496,"date":"2024-02-09T00:00:00","date_gmt":"2024-02-09T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1344051"},"modified":"2024-02-09T00:00:00","modified_gmt":"2024-02-09T00:00:00","slug":"case-report-preimplantation-genetic-testing-for-infantile-gm1-gangliosidosis","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2024\/02\/09\/case-report-preimplantation-genetic-testing-for-infantile-gm1-gangliosidosis\/","title":{"rendered":"Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis"},"content":{"rendered":"<p>Ganglioside-monosialic acid (GM1) gangliosidosis (ICD-10: E75.1; OMIM: 230500, 230600, 230650) is a rare autosomal recessive hereditary disease, lysosomal storage disorder caused by mutations in the <italic>GLB1<\/italic> gene that lead to the absence or insufficiency of \u03b2-galactosidase. In this study, we report a case of a Russian family with a history of GM1 gangliosidosis. The family had a child who, from the age of 6\u00a0months, experienced a gradual loss of developmental skills, marked by muscle flaccidity, psychomotor retardation, hepatosplenomegaly, and the onset of tonic seizures by the age of 8\u00a0months. Funduscopic examination revealed a \u00abcherry red spot\u00bb in the macula, which is crucial for the diagnosis of lipid storage disorders. To find the pathogenic variants responsible for these clinical symptoms, the next-generation sequencing approach was used. The analysis revealed two variants in the heterozygous state: a frameshift variant c.699delG (rs1452318343, ClinVar ID 928700) in exon 6 and a missense variant c.809A&gt;C (rs371546950, ClinVar ID 198727) in exon 8 of the <italic>GLB1<\/italic> gene. The spouses were advised to plan the pregnancy with assisted reproductive technology (ART), followed by preimplantation genetic testing for monogenic disorder (PGT-M) on the embryos. Trophectoderm biopsy was performed on 8 out of 10 resulting embryos at the blastocyst stage. To perform PGT-M, we developed a novel testing system, allowing for direct analysis of disease-causing mutations, as well as haplotype analysis based on the study of polymorphic markers\u2014short tandem repeats (STR), located upstream and downstream of the <italic>GLB1<\/italic> gene. The results showed that four embryos were heterozygous carriers of pathogenic variants in the <italic>GLB1<\/italic> gene (#1, 2, 5, 8). Two embryos had a compound heterozygous genotype (#3, 4), while the embryos #7 and 9 did not carry disease-causing alleles of the <italic>GLB1<\/italic> gene. The embryo #7 without pathogenic variants was transferred after consideration of its morphology and growth rate. Prenatal diagnosis in the first trimester showed the absence of the variants analyzed in the <italic>GLB1<\/italic> gene in the fetus. The pregnancy resulted in the delivery of a female infant who did not inherit the disease-causing variants in the <italic>GLB1<\/italic> gene.<\/p>","protected":false},"excerpt":{"rendered":"<p>Ganglioside-monosialic acid (GM1) gangliosidosis (ICD-10: E75.1; OMIM: 230500, 230600, 230650) is a rare autosomal recessive hereditary disease, lysosomal storage disorder caused by mutations in the GLB1 gene that lead to the absence or insufficiency o&#8230;<\/p>\n","protected":false},"author":102,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,12,13],"tags":[],"class_list":["post-496","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\/496","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\/102"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=496"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/496\/revisions"}],"predecessor-version":[{"id":497,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/496\/revisions\/497"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=496"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=496"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=496"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}