Anti-ST3GAL5 monoclonal antibody, clone 9C5

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.

Background: Milk sialylated oligosaccharides (SOS) play crucial roles in many biological processes. The most abundant free SOS in goat's milk are 3'sialyllactose (3'-SL), 6'sialyllactose (6'-SL) and disialyllactose (DSL). The production of these molecules is determined genetically by the expression of glycosyltransferases and by the availability of nucleotide sugar substrates, but the precise mechanisms regulating the differential patterns of milk oligosaccharides are not known. We aimed to identify the complete cDNAs of candidate genes implicated in SOS biosynthesis (B4GALT1, LALBA, ST3GAL5, ST6GAL1) and to analyse their expression during lactation in the Garganica and Maltese goat breeds. Moreover, we analysed the colostrum and milk contents of 3'-SL, 6'-SL and disialyllactose (DSL) and the possible correlations between expressed genes and SOS. Results: We identified the complete coding cDNAs of B4GALT1 (HQ700335.1), ST3GAL5 (KF055858.2), and ST6GAL1 (HQ709167.1), the single nucleotide polymorphism (SNPs) of these genes and 2 splicing variants of the ST6GAL1 cDNA. RT-qPCR analysis showed that LALBA and ST6GAL1 were the genes with the highest and lowest expression in both breeds, respectively. The interaction effects of the breeds and sampling times were associated with higher levels of B4GALT1 and ST3GAL5 gene expression in Garganica than in Maltese goats at kidding. B4GALT1, LALBA, and ST3GAL5 gene expression changed from kidding to 60 and 120 days in Maltese goats, while in Garganica goats, a difference was observed only for the LALBA gene. Breed and lactation effects were also found for SOS contents. Positive correlations of B4GALT1, LALBA, ST3GAL5, and ST6GAL1 with 3'-SL/6'SL and DSL were found. Conclusions: The genetic effect on the oligosaccharide content of milk was previously highlighted in bovines, and this study is the first to investigate this effect in two goat breeds (Garganica and Maltese) during lactation. The genetic variability of candidate genes involved in SOS biosynthesis highlights their potential role in affecting gene expression and ultimately biological function. The investigation of gene regulatory regions as well as the examination of other sialyltransferase genes will be needed to identify the genetic pattern leading to a higher SOS content in the autochtonous Garganica breed and to protect it using a focused breeding strategy.