{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:52:05Z","timestamp":1781671925140,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Sciences of the Republic of Tatarstan","award":["12\/2025-PD-KFU"],"award-info":[{"award-number":["12\/2025-PD-KFU"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by a deficiency of \u03b2-galactosidase due to pathogenic variants in the GLB1 gene. Almost 300 pathogenic or likely pathogenic variants have been identified, associated with a phenotypic spectrum ranging from GM1 gangliosidosis to mucopolysaccharidosis type IVB. Disease severity is largely determined by the extent to which specific variants impair enzymatic catalytic activity, particularly through disruption of substrate recognition and binding within the active site. We report a patient with GM1 gangliosidosis type I harboring two pathogenic missense variants, c.808T&gt;G (p.Tyr270Asp) and c.808T&gt;C (p.Tyr270His), in a compound heterozygous state. To the best of our knowledge, this specific allelic combination has not been previously described. Both variants affect the same codon, resulting in distinct amino acid substitutions at position 270, a residue critically involved in maintaining the structural and functional integrity of the catalytic domain of \u03b2-galactosidase. Disruption at this site is expected to severely compromise enzymatic activity. Comparative analysis with previously reported cases carrying variants at the same residue, in either homozygous or compound heterozygous states, demonstrates a possible consistent association with the infantile form of GM1 gangliosidosis, characterized by a rapidly progressive neurodegenerative course and multisystem involvement. Collectively, these findings provide additional support for the hypothesis that codon 270 can be regarded as a critical functional hotspot within GLB1, where even distinct amino acid substitutions can result in profound enzymatic dysfunction and a severe early-onset phenotype.<\/jats:p>","DOI":"10.3390\/genes17060691","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:27:21Z","timestamp":1781666841000},"page":"691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Infantile GM1 Gangliosidosis with Epilepsy Associated with a Same-Codon GLB1 Variant (c.808T&gt;G\/c.808T&gt;C)"],"prefix":"10.3390","volume":"17","author":[{"given":"Rimma","family":"Gamirova","sequence":"first","affiliation":[{"name":"Neurocognitive Research Laboratory, Department of Neurology with Courses in Psychiatry, Clinical Psychology, and Medical Genetics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlevskaya St., Kazan 420008, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-1494","authenticated-orcid":false,"given":"Arina","family":"Grishagina","sequence":"additional","affiliation":[{"name":"Neurocognitive Research Laboratory, Department of Neurology with Courses in Psychiatry, Clinical Psychology, and Medical Genetics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlevskaya St., Kazan 420008, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gorobets","sequence":"additional","affiliation":[{"name":"Neurocognitive Research Laboratory, Department of Applied and Experimental Linguistics, Center for Speech Pathology, Kazan (Volga Region) Federal University, 18 Kremlevskaya St., Kazan 420008, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0624-3038","authenticated-orcid":false,"given":"Giuditta","family":"Bargiacchi","sequence":"additional","affiliation":[{"name":"Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-7597","authenticated-orcid":false,"given":"Marco","family":"Carotenuto","sequence":"additional","affiliation":[{"name":"Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ymgme.2019.12.012","article-title":"The Natural History of Type 1 Infantile GM1 Gangliosidosis: A Literature-Based Meta-Analysis","volume":"129","author":"Lang","year":"2020","journal-title":"Mol. 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