Coutinho, M.F.Lacerda, L.Pinto, E.Ribeiro, H.Macedo-Ribeiro, S.Castro, L.Prata, M.J.Alves, S.2015-02-132015-02-132014-08-04Clin Genet. 2014 Aug 4. doi: 10.1111/cge.12469. Epub 2014 Sep 17.0009-9163http://hdl.handle.net/10400.18/2850The newly-synthesized lysosomal enzymes travel to the trans-Golgi network (TGN) and are then driven to the acidic organelle. While the best-known pathway for TGN-to-endosome transport is the delivery of soluble hydrolases by the M6P receptors (MPRs), additional pathways do exist, as showed by the identification of two alternative receptors: LIMP-2, implicated in the delivery of β-glucocerebrosidase; and sortilin, involved in the transport of the sphingolipid activator proteins prosaposin and GM2AP, acid sphingomyelinase and cathepsins D and H. Disruption of the intracellular transport and delivery pathways to the lysosomes may result in lysosomal dysfunction, predictably leading to a range of clinical manifestations of lysosomal storage diseases. However, for a great percentage of patients presenting such manifestations, no condition is successfully diagnosed. To analyse if, in this group, phenotypes could be determined by impairments in the known M6P-independent receptors, we screened the genes that encode for LIMP-2 and sortilin. No pathogenic mutations were identified. Other approaches will be needed to clarify whether sortilin dysfunction may cause disease.engDoenças GenéticasGenética HumanaDoenças Lisossomais de SobrecargaLIMP-2M6P Independent TraffickingLysosomal Storage DiseasesSortilinjournal article10.1111/cge.12469