Identification and characterization of six new mutations in GLB1 gene in Ukrainian patients with GM1 gangliosidosis and Morquio B disease

Mytsyk, N. Y.; Горовенко, Н. Г.

doi:10.7124/bc.00093c

Cited by 2 publications

(2 citation statements)

References 20 publications

(8 reference statements)

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“…Two gypsy patients had p.R59H homozygous mutation but other patients had p.R201H, p.L155R, p Were S434L, and p.G554E 58 . Similar to this study, Mytsyk et al examined the glb1 gene in 25 Ukrainian patients with GM1 gangliosidosis and Morquio B syndrome, and 52 alleles were studied, resulting in 17 mutations that cause the disease, including 11 missense replacement mutations an insertion mutation, three deletion mutations, and two splicing site mutations (such as VS12 + 8 T > C) 59 . Caciotti et al Studied 21 unrelated patients with GM1 gangliosidosis with a mutation in the glb1 gene, and the mutation analysis showed that one of the patients with the infantile allele phenotype of glb1 contained two genetic variants that resulted in amino acid changes of p. R68W and p. R109W.…”

Section: Introductionsupporting

confidence: 57%

Gene therapy approaches for GM1 gangliosidosis: Focus on animal and cellular studies

Hosseini,

Fallahi,

Tabei

et al. 2023

Cell Biochemistry & Function

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One of the most important inherited metabolic disorders is GM1 gangliosidosis, which is a progressive neurological disorder. The main cause of this disease is a genetic defect in the enzyme β‐galactosidase due to a mutation in the glb1 gene. Lack of this enzyme in cells (especially neurons) leads to the accumulation of ganglioside substrate in nerve tissues, followed by three clinical forms of GM1 disease (neonatal, juvenile, and adult variants). Genetically, many mutations occur in the exons of the glb1 gene, such as exons 2, 6, 15, and 16, so the most common ones reported in scientific studies include missense/nonsense mutations. Therefore, many studies have examined the genotype‐phenotype relationships of this disease and subsequently using gene therapy techniques have been able to reduce the complications of the disease and alleviate the signs and symptoms of the disease. In this regard, the present article reviews the general features of GM1 gangliosidosis and its mutations, as well as gene therapy studies and animal and human models of the disease.

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Section: Introductionsupporting

confidence: 57%

Gene therapy approaches for GM1 gangliosidosis: Focus on animal and cellular studies

Hosseini,

Fallahi,

Tabei

et al. 2023

Cell Biochemistry & Function

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“…The variant rs1452318343 was reported in gnomAD, ClinVar, and RUSeq (cohort of diseased individuals) databases (Barbitoff et al, 2021). Previously it was found in multiple patients with infantile form of GM1 gangliosidosis from Ukraine (Mytsyk and Gorovenko, 2016). The variant rs371546950 was not described in any of the analyzed databases.…”

Section: Discussionmentioning

confidence: 99%

Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis

Zagaynova,

Nasykhova,

Tonyan

et al. 2024

Front. Genet.

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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 of β-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 months, 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 months. Funduscopic examination revealed a «cherry red spot» 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>C (rs371546950, ClinVar ID 198727) in exon 8 of the GLB1 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—short tandem repeats (STR), located upstream and downstream of the GLB1 gene. The results showed that four embryos were heterozygous carriers of pathogenic variants in the GLB1 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 GLB1 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 GLB1 gene in the fetus. The pregnancy resulted in the delivery of a female infant who did not inherit the disease-causing variants in the GLB1 gene.

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Identification and characterization of six new mutations in GLB1 gene in Ukrainian patients with GM1 gangliosidosis and Morquio B disease

Cited by 2 publications

References 20 publications

Gene therapy approaches for GM1 gangliosidosis: Focus on animal and cellular studies

Gene therapy approaches for GM1 gangliosidosis: Focus on animal and cellular studies

Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis

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