Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganglioside GM3 is the predominant ganglioside of keratinocyte membranes. It has been proposed in other cell types that GM3 may participate in the regulation of cell proliferation. To examine the role of GM3 in keratinocyte proliferation, purified GM3 was added to cultured keratinocytes from normal foreskin, from lesional skin of patients with psoriasis and ichthyosis, and to cutaneous squamous carcinoma cell lines. Supplemental GM3 inhibited the growth of all cultured keratinocytes in a dose-dependent manner at concentrations of 10-100 microM. Keratinocytes from patients with psoriasis and ichthyosis were most sensitive to the inhibitory effects of GM3, and confluent undifferentiated keratinocytes were least sensitive. No change in differentiation was noted after addition of GM3. GD3, 9-0-acetyl-GD3, and GD1b also inhibited keratinocyte proliferation. Gangliosides GM1 and GD1a and sialic acid had little effect. Addition of 50 microM 3H-GM3 to cultured keratinocytes resulted in 1.7 times the amount of cellular GM3. These data suggest that hematoside (GM3) and "b" pathway gangliosides (GD3, GD1b), generated by the preferential activation of sialyltransferase II versus N-acetylgalactosaminyltransferase, may be involved in control of keratinocyte growth but not of differentiation.
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PMID:Ganglioside GM3 inhibits the proliferation of cultured keratinocytes. 849 25

GM3 synthase deficiency is due to biallelic pathogenic variants in ST3GAL5, which encodes a sialyltransferase that synthesizes ganglioside GM3. Key features of this rare autosomal recessive condition include profound intellectual disability, failure to thrive and infantile onset epilepsy. We expand the phenotypic spectrum with 3 siblings who were found by whole exome sequencing to have a homozygous pathogenic variant in ST3GAL5, and we compare these cases to those previously described in the literature. The siblings had normal birth history, subsequent developmental stagnation, profound intellectual disability, choreoathetosis, failure to thrive, and visual and hearing impairment. Ichthyosis and self-injurious behavior are newly described in our patients and may influence clinical management. We conclude that GM3 synthase deficiency is a neurodevelopmental disorder with consistent features of profound intellectual disability, choreoathetosis, and deafness. Other phenotypic features have variable expressivity, including failure to thrive, epilepsy, regression, vision impairment, and skin findings. Our analysis demonstrates a broader phenotypic range of this potentially under-recognized disorder.
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PMID:ST3GAL5-Related Disorders: A Deficiency in Ganglioside Metabolism and a Genetic Cause of Intellectual Disability and Choreoathetosis. 3018 2