{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:56Z","timestamp":1753891196384,"version":"3.41.2"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"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. Genet."],"abstract":"<jats: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 <jats:italic>GLB1<\/jats: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&amp;gt;C (rs371546950, ClinVar ID 198727) in exon 8 of the <jats:italic>GLB1<\/jats: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 <jats:italic>GLB1<\/jats:italic> gene. The results showed that four embryos were heterozygous carriers of pathogenic variants in the <jats:italic>GLB1<\/jats: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 <jats:italic>GLB1<\/jats: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 <jats:italic>GLB1<\/jats: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 <jats:italic>GLB1<\/jats:italic> gene.<\/jats:p>","DOI":"10.3389\/fgene.2024.1344051","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T04:52:16Z","timestamp":1707454336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis"],"prefix":"10.3389","volume":"15","author":[{"given":"Valeria A.","family":"Zagaynova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia A.","family":"Nasykhova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziravard N.","family":"Tonyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria M.","family":"Danilova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya M.","family":"Dvoynova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana E.","family":"Lazareva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana E.","family":"Ivashchenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena S.","family":"Shabanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna O.","family":"Krikheli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Lesik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olesya N.","family":"Bespalova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Yu.","family":"Kogan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey S.","family":"Glotov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1101\/2021.11.02.21265801","article-title":"Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 7,452 exome samples","author":"Barbitoff","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1177\/0883073807307088","article-title":"Brain proton magnetic resonance spectroscopy and neuromuscular pathology in a patient with GM1 gangliosidosis","volume":"23","author":"Brunetti-Pierri","year":"2008","journal-title":"J. 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