Targeted gene(s)/phenotype under study
By trio-based exome sequencing, we identified compound heterozygous missense variants in B4GALT5 gene (p.Gly274Arg, p.Arg173His) in a patient with bilateral cataracts, intellectual disability, hypermobility joints and marfanoid habitus. The p.Gly274Arg variant is present in 1/251,428 in GnomAD controls while the variant p.Arg173His is absent in GnomAD.
The gene is sensitive to either missense variants and to loss-of-function variants. B4GALT5 encodes for B4GalT5 enzyme involved in sphingolipid metabolism, allowing the conversion of glucosyl-ceramide to lactosyl-ceramide, which is then transformed into ganglioside GM3. The sphingolipids profile in the proband showed high levels of glucosyl-ceramide while low levels of lactosyl-ceramide and ganglioside GM3 were detected supporting a B4GalT5 deficiency. These data might support a novel condition associated to B4GalT5 deficiency and we are looking for other patients sharing clinical features and variants in B4GALT5.
Federico II University
Department of Translational Medicine
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples : Yes
- Resampling of patients : No
- Linked to a translational/basic research project? Yes