Targeted gene(s)/phenotype under study

B4GALT5 (604016)


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.

Coordinating clinicians/researchers

Nicola Brunetti-Pierri


Federico II University
Department of Translational Medicine
Naples, Italy

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