Expression and characterization of 14 GLB1 mutant alleles found in GM1-gangliosidosis and Morquio B patients

GM1-gangliosidosis and Morquio B disease are lysosomal storage disorders caused by β-galactosidase deficiency attributable to mutations in the GLB1 gene. On reaching the endosomal-lysosomal compartment, the β-galactosidase protein associates with the protective protein/cathepsin A (PPCA) and neuraminidase proteins to form the lysosomal multienzyme complex (LMC). The correct interaction of these proteins in the complex is essential for their activity. More than 100 mutations have been described in GM1-gangliosidosis and Morquio B patients, but few have been further characterized. We expressed 12 mutations suspected to be pathogenic, one known polymorphic change (p.S532G), and a variant described as either a pathogenic or a polymorphic change (p.R521C). Ten of them had been expressed The the of the 12 the of is with as a The for change is a the of these β-galactosidase the by and The of neuraminidase and in of the protein the is in GM1-gangliosidosis and Morquio B GM1-gangliosidosis and Morquio B disease are lysosomal storage disorders caused by β-galactosidase deficiency attributable to mutations in the GLB1 gene. On reaching the endosomal-lysosomal compartment, the β-galactosidase protein associates with the protective protein/cathepsin A (PPCA) and neuraminidase proteins to form the lysosomal multienzyme complex (LMC). The correct interaction of these proteins in the complex is essential for their activity. More than 100 mutations have been described in GM1-gangliosidosis and Morquio B patients, but few have been further characterized. We expressed 12 mutations suspected to be pathogenic, one known polymorphic change (p.S532G), and a variant described as either a pathogenic or a polymorphic change (p.R521C). Ten of them had been expressed The the of the 12 the of is with as a The for change is a the of these β-galactosidase the by and The of neuraminidase and in of the protein the is in GM1-gangliosidosis and Morquio B The deficiency of lysosomal β-galactosidase caused by mutations in the GLB1 is the of the lysosomal storage disorders GM1-gangliosidosis in and Morquio B disease in for β-galactosidase are and The is the in GM1-gangliosidosis patients, and the is the in Morquio B to of and of have been in GM1-gangliosidosis and The in are attributable to of the to of in β-galactosidase in patients, the of in to in the form and to in Morquio B have but as a of a of of in with Morquio B GLB1 to of to by in to a of the β-galactosidase and a of the protein The β-galactosidase protein is to the as is to a is a of the in and The variant of is to the complex of and protective protein/cathepsin A The β-galactosidase protein a the lysosomal multienzyme complex reaching the endosomal-lysosomal compartment, the associates with the and complex the The correct interaction of these proteins in the complex is essential for their correct multienzyme and the a protective for lysosomal but in the correct of β-galactosidase to the form of the of the form a complex in is by the protective protein/cathepsin lysosomal protective and with in the described mutations in GM1-gangliosidosis and Morquio B mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with of them their in 100 are the their in by for 12 a (p.S532G), and a change pathogenic (p.R521C). Ten of these had been expressed the 12 mutations caused a or a of and in activity. and be of β-galactosidase of the and in to GM1-gangliosidosis or Morquio B described by mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with The and of are in and of in are described in for described in of in are described in mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the for described in of GLB1 in with of in in a of the GLB1 by in and in a in the protein the and the and of and the and mutations by the to the the of the the in a the to had been and in 100 with and with and β-galactosidase the of the with of a a β-galactosidase by and for with of the for The the as described mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the and protein by the in and the with the and to and of protein for as described of in disease pathogenic and The of the β-galactosidase described The variant of is to the with of a of the in and by the for in the of 100 of of and of interaction β-galactosidase and by with of and with of the described of protein in by with the to the for the and of protein for with of The and the and as described of lysosomal neuraminidase to protective protein/cathepsin to with the and the as the to of the to the for as as for the and for as a The of expressed as a of the of the of the in the and the described The to in of and of and β-galactosidase in of the GLB1 expressed in to their The expressed (p.S532G), and the The expressed of β-galactosidase in the with The for as a of is in The in of the and with and of the of the of with of and of them and the of the for for mutations and The change described as a mutations in with and as a of and protein in lysosomal and of with mutations but the the of the in with of and the of in a of expressed a correct of the proteins the in in in of of the and the variant proteins A of in a β-galactosidase to the a of protein in as and of for of the lysosomal and a to be to the in of the The in of the expressed of expressed mutations in The to with A of of protein in of β-galactosidase with proteins in been of lysosomal neuraminidase to protective protein/cathepsin the and β-galactosidase with neuraminidase and and β-galactosidase with to the mutations in the the of The are in the β-galactosidase the the or the or the a of these of protein with neuraminidase in the in mutations the interaction of the are are as protein of protective protein/cathepsin A and neuraminidase of protein of and neuraminidase of β-galactosidase and expressed of and expressed are the mutations and A of of protein for of the of mutations the proteins of the and protein of are in of β-galactosidase neuraminidase and are the are for the the is A of of protein in the to a of to the form of the A to the the for the than for the a for and to with the described of caused by of the of lysosomal neuraminidase the of the storage of a in the for for the neuraminidase the for the of the to the form of the as as the and a of to a for of the The in and to the than mutations GM1-gangliosidosis or Morquio B disease have been described in the GLB1 but few of them have been expressed to their to be in or with the in of the are to the of have been and to lysosomal in lysosomal to to the of the in of the of expressed mutations in the of the mutations The are are with in of the be few of these the of expressed The for are described is of by and in with a the by mutations in with to a for the the for the as the of expressed is to the of with the of protein for and of and of the are than described for the with the with these of the in expressed in and of the in expressed in and are of and protein in lysosomal and of with of and protein in lysosomal and of with and of a with Morquio B mutations in a and of the of the in the GLB1 of a and of in deficiency GM1-gangliosidosis of mutations in and of the mutations in with of and protein in lysosomal and of with of mutations and and a in a of of mutations and and a in a of in GM1-gangliosidosis in and are in a The of change is described as a and in of a mutations in with and in of mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of and protein in lysosomal and of with described a for change in to be the the change in of activity. is of the but is of of the mutations the of the the but with a change have been to as the of the disease in a a few patients, the one by of and protein in lysosomal and of with attributable to in or the the change be a A is the in of in in a had the of the disease and a of the a as with be pathogenic in a the polymorphic change in of is a in the the expressed mutations and the of the The and in patients, had activity. The mutations in patients, and had and of in Morquio B are to have the of but of in with Morquio B is for of activity. The in Morquio B patients, had the be the Morquio as mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the to for mutations and in Morquio B one of them have activity. and had to as the Morquio be to in for of the expressed be to the of correct or a protein as by the of of of the variant proteins to be be either a the or a of the The to be of the mutations expressed in the are described as essential for the of as the of lysosomal by and of mutations and and a in a of of the β-galactosidase mutations and the with the proteins the by β-galactosidase with of the of interaction β-galactosidase and The in of the mutations the interaction of the to the of the mutations the protein the the by of protein or for β-galactosidase mutations in and the of a β-galactosidase protein of is these either or mutations of a be to to proteins with these patients, as in in their the of mutations and to but by the to to a protein of in to the form of the The protein to the be The caused by the in in a the of a of in the protein to of the the a be the for the with and in patients, the for these proteins a of neuraminidase and a of the for and the with the of the had in the of the The for the and neuraminidase mutations in the β-galactosidase protein the of the proteins in the GM1-gangliosidosis neuraminidase of the than in or patients, is of The deficiency of lysosomal β-galactosidase caused by mutations in the GLB1 is the of the lysosomal storage disorders GM1-gangliosidosis in and Morquio B disease in for β-galactosidase are and The is the in GM1-gangliosidosis patients, and the is the in Morquio B to of and of have been in GM1-gangliosidosis and The in are attributable to of the to of in β-galactosidase in patients, the of in to in the form and to in Morquio B have but as a of a of of in with Morquio B The GLB1 to of to by in to a of the β-galactosidase and a of the protein The β-galactosidase protein is to the as is to a is a of the in and The variant of is to the complex of and protective protein/cathepsin A The β-galactosidase protein a the lysosomal multienzyme complex reaching the endosomal-lysosomal compartment, the associates with the and complex the The correct interaction of these proteins in the complex is essential for their correct multienzyme and the a protective for lysosomal but in the correct of β-galactosidase to the form of the of the form a complex in is by the protective protein/cathepsin lysosomal protective and with in the described mutations in GM1-gangliosidosis and Morquio B mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with of them their in 100 are the their in by for 12 a (p.S532G), and a change pathogenic (p.R521C). Ten of these had been expressed the 12 mutations caused a or a of and in activity. and be of β-galactosidase of the and in to GM1-gangliosidosis or Morquio B described by mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with The and of are in and of in are described in for described in of in are described in mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the for described in of GLB1 in with of in in a of the GLB1 by in and in a in the protein the and the and of and the and mutations by the to the the of the the in a the to had been and in 100 with and with and β-galactosidase the of the with of a a β-galactosidase by and for with of the for The the as described mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the and protein by the in and the with the and to and of protein for as described of in disease pathogenic and The of the β-galactosidase described The variant of is to the with of a of the in and by the for in the of 100 of of and of interaction β-galactosidase and by with of and with of the described of protein in by with the to the for the and of protein for with of The and the and as described of lysosomal neuraminidase to protective protein/cathepsin to with the and the as the to of the to the for as as for the and for as a The of expressed as a of the of the of the in the and the described The to in of and in to GM1-gangliosidosis or Morquio B described by mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with The and of are in and of in are described in for described in of in are described in mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the for described in of GLB1 in with of in in a The and in to GM1-gangliosidosis or Morquio B described by mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of GLB1 in with The and of are in of the GLB1 by in and in a in the protein the and the and of and the and The of the GLB1 by in and in a in the protein the and the and of and the and mutations by the to the the of the the in a the to had been mutations by the to the the of the the in a the to had been and in 100 with and with and β-galactosidase the of the with of a a β-galactosidase by and for with of the for The the as described mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the and protein by the in and the in 100 with and with and β-galactosidase the of the with of a a β-galactosidase by and for with of the for The the as described mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the and protein by the in and the with the with the and to and of protein for as described of in disease pathogenic and The of the β-galactosidase described The variant of is to the with of a of the in and by the for in the of 100 of of and of to and of protein for as described of in disease pathogenic and The of the β-galactosidase described The variant of is to the with of a of the in and by the for in the of 100 of of and of interaction β-galactosidase and by with of and with of the described of protein in by with the to the for the and of protein for with of The and the and as described of lysosomal neuraminidase to protective protein/cathepsin to with the and the as the to of the to the The interaction β-galactosidase and by with of and with of the described of protein in by with the to the for the and of protein for with of The and the and as described of lysosomal neuraminidase to protective protein/cathepsin to with the and the as the to of the to the for as as for the and for as a The of expressed as a of the of the of the in the and the described The to in of for as as for the and for as a The of expressed as a of the of the of the in the and the described The to in of and of and β-galactosidase in of the GLB1 expressed in to their The expressed (p.S532G), and the The expressed of β-galactosidase in the with The for as a of is in The in of the and with and of the of the of with of and of them and the of the for for mutations and The change described as a mutations in with and as a of and protein in lysosomal and of with mutations but the the of the in with of and the of in a of expressed a correct of the proteins the in in in of of the and the variant proteins A of in a β-galactosidase to the a of protein in as and of for of the lysosomal and a to be to the in of the The in of the expressed of β-galactosidase with proteins in been of lysosomal neuraminidase to protective protein/cathepsin the and β-galactosidase with neuraminidase and and β-galactosidase with to the mutations in the the of The are in the β-galactosidase the the or the or the a of these of protein with neuraminidase in the in mutations the interaction of the are are as protein of protective protein/cathepsin A and neuraminidase of protein of and neuraminidase of β-galactosidase and expressed of and expressed are the mutations and A of of protein for of the of mutations the proteins of the and protein of are in of β-galactosidase neuraminidase and are the are for the the is A of of protein in the to a of to the form of the A to the the for the than for the a for and to with the described of caused by of the of lysosomal neuraminidase the of the storage of a in the for for the neuraminidase the for the of the to the form of the as as the and a of to a for of the The in and to the and of and β-galactosidase in of the GLB1 expressed in to their The expressed (p.S532G), and the The expressed of β-galactosidase in the with The for as a of is in The in of the and with and of the of the of with of and of them and the of the for for mutations and The change described as a mutations in with and as a of and protein in lysosomal and of with mutations but the the of the in with of and the of in a of the GLB1 expressed in to their The expressed (p.S532G), and the The expressed of β-galactosidase in the with The for as a of is in The in of the and with and of the of the of with of and of them and the of the for for mutations and The change described as a mutations in with and as a of and protein in lysosomal and of with mutations but the the activity. of of expressed a correct of the proteins the in in in of of the and the variant proteins A of in a β-galactosidase to the a of protein in as and of for of the lysosomal and a to be to the in of the The in of the expressed a correct of the proteins the in in in of of the and the variant proteins A of in a β-galactosidase to the a of protein in as and of for of the lysosomal and a to be to the in of the The in of the expressed of β-galactosidase with proteins in been of lysosomal neuraminidase to protective protein/cathepsin the and β-galactosidase with neuraminidase and and β-galactosidase with to the mutations in the the of The are in the β-galactosidase the the or the or the a of these of protein with neuraminidase in the in mutations the interaction of the The of β-galactosidase with proteins in been of lysosomal neuraminidase to protective protein/cathepsin the and β-galactosidase with neuraminidase and and β-galactosidase with to the mutations in the the of The are in the β-galactosidase the the or the or the a of these of protein with neuraminidase in the in mutations the interaction of the of the of mutations the proteins of the and protein of are in the to a of to the form of the A to the the for the than for the a for and to with the described of caused by of the of lysosomal neuraminidase the of the storage of a in the for for the neuraminidase the for the of the to the form of the as as the and a of to a for of the The in and to the the of mutations the proteins of the and protein of are in the to a of to the form of the A to the the for the than for the a for and to with the described of caused by of the of lysosomal neuraminidase the of the storage of a in the for for the neuraminidase the for the of the to the form of the as as the and a of to a for of the The in and to the than mutations GM1-gangliosidosis or Morquio B disease have been described in the GLB1 but few of them have been expressed to their to be in or with the in of the are to the of have been and to lysosomal in lysosomal to to the of the in of the of expressed mutations in the of the mutations The are are with in of the be few of these the of expressed The for are described is of by and in with a the by mutations in with to a for the the for the as the of expressed is to the of with the of protein for and of and of the are than described for the with the with these of the in expressed in and of the in expressed in and are of and protein in lysosomal and of with of and protein in lysosomal and of with and of a with Morquio B mutations in a and of the of the in the GLB1 of a and of in deficiency GM1-gangliosidosis of mutations in and of the mutations in with of and protein in lysosomal and of with of mutations and and a in a of of mutations and and a in a of in GM1-gangliosidosis in and are in a The of change is described as a and in of a mutations in with and in of mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of and protein in lysosomal and of with described a for change in to be the the change in of activity. is of the but is of of the mutations the of the the but with a change have been to as the of the disease in a a few patients, the one by of and protein in lysosomal and of with attributable to in or the the change be a A is the in of in in a had the of the disease and a of the a as with be pathogenic in a the polymorphic change in of is a in the the expressed mutations and the of the The and in patients, had activity. The mutations in patients, and had and of in Morquio B are to have the of but of in with Morquio B is for of activity. The in Morquio B patients, had the be the Morquio as mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the to for mutations and in Morquio B one of them have activity. and had to as the Morquio be to in for of the expressed be to the of correct or a protein as by the of of of the variant proteins to be be either a the or a of the The to be of the mutations expressed in the are described as essential for the of as the of lysosomal by and of mutations and and a in a of of the β-galactosidase mutations and the with the proteins the by β-galactosidase with of the of interaction β-galactosidase and The in of the mutations the interaction of the to the of the mutations the protein the the by of protein or for β-galactosidase mutations in and the of a β-galactosidase protein of is these either or mutations of a be to to proteins with these patients, as in in their the of mutations and to but by the to to a protein of in to the form of the The protein to the be The caused by the in in a the of a of in the protein to of the the a be the for the with and in patients, the for these proteins a of neuraminidase and a of the for and the with the of the had in the of the The for the and neuraminidase mutations in the β-galactosidase protein the of the proteins in the GM1-gangliosidosis neuraminidase of the than in or patients, is of More than mutations GM1-gangliosidosis or Morquio B disease have been described in the GLB1 but few of them have been expressed to their to be in or with the in of the are to the of have been and to lysosomal in lysosomal to to the of the in of the of expressed mutations in the of the mutations The are are with in of the be few of these the of expressed The for are described is of by and in with a the by mutations in with to a for the the for the as the of expressed is to the of with the of protein for and of and of the are than described for the with the with these The of change is described as a and in of a mutations in with and in of mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the of and protein in lysosomal and of with described a for change in to be the the change in of activity. is of the but is of of the mutations the of the the but with a change have been to as the of the disease in a a few patients, the one by of and protein in lysosomal and of with attributable to in or the the change be a A is the in of in in a had the of the disease and a of the a as with be pathogenic in a the polymorphic change in of is a in the the expressed mutations and the of the The and in patients, had activity. The mutations in patients, and had and of in Morquio B are to have the of but of in with Morquio B is for of activity. The in Morquio B patients, had the be the Morquio as mutations in the GLB1 in a of GM1-gangliosidosis and Morquio B for the to for mutations and in Morquio B one of them have activity. and had to as the Morquio be to The in for of the expressed be to the of correct or a protein as by the of of of the variant proteins to be be either a the or a of the The to be of the mutations expressed in the are described as essential for the of as the of lysosomal by and of mutations and and a in a of The of the β-galactosidase mutations and the with the proteins the by β-galactosidase with of the of interaction β-galactosidase and The in of the mutations the interaction of the A to the of the mutations the protein the the by of protein or The for β-galactosidase mutations in and the of a β-galactosidase protein of is these either or mutations of a be to to proteins with these patients, as in in their the of mutations and to but by the to to a protein of in to the form of the The protein to the be The caused by the in in a the of a of in the protein to of the the a be the for the with and in patients, the for these proteins a of neuraminidase and a of the for and the with the of the had in the of the The for the and neuraminidase mutations in the β-galactosidase protein the of the proteins in the GM1-gangliosidosis neuraminidase of the than in or patients, is of is the of a the of The and for The are to for the by and and and

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.