Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles

Serena Grossi; Stefano Regis; Camillo Rosano; Fabio Corsolini; Graziella Uziel; Maria Sessa; Maja Di Rocco; Giancarlo Parenti; Federica Deodato; Vincenzo Leuzzi; Roberta Biancheri; Mirella Filocamo

doi:10.1002/humu.20851

Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles

Serena Grossi, Stefano Regis, Camillo Rosano, Fabio Corsolini, Graziella Uziel, Maria Sessa, Maja Di Rocco, Giancarlo Parenti, Federica Deodato, Vincenzo Leuzzi, Roberta Biancheri, Mirella Filocamo

Research output: Contribution to journal › Article › peer-review

Abstract

Metachromatic leukodystrophy (MLD), the demyelinating disorder resulting from impaired sulfatide catabolism, is caused by allelic mutations of the Arylsulfatase A (ARSA) locus except for extremely rare cases of Saposin-B (Sap-B) deficiency. We characterized twenty-one unrelated Italian patients among which seventeen were due to ARSA activity deficiency and 4 others resulted from Saposin-B defect. Overall, we found 20 different mutant ARSA alleles and 2 different Sap-B alleles. The eleven new ARSA alleles (c.53C>A; c.88G>C; c.372G>A; c.409_411delCCC; c.634G>C; [c.650G>A;c.1108C>T]; c.845A>G; c.906G>C; c.919G>T; c.1102-3C>G; c.1126T>A) were functionally characterized and the novel amino acid changes were also modelled into the three-dimensional structure. The present study is aimed at providing a broader picture of the molecular basis of MLD in the Italian population. It also emphasizes the importance of a comprehensive evaluation in MLD diagnosis including biochemical, enzymatic and molecular investigations.

Original language	English
Journal	Human Mutation
Volume	29
Issue number	11
DOIs	https://doi.org/10.1002/humu.20851
Publication status	Published - Nov 2008

Keywords

ARSA
Arylsulfatase A
Demyelinating disorder
Functional study
Metachromatic leukodystrophy
MLD
Modelling
Molecular analysis
Saposin-B

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/humu.20851

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Grossi, S., Regis, S., Rosano, C., Corsolini, F., Uziel, G., Sessa, M., Di Rocco, M., Parenti, G., Deodato, F., Leuzzi, V., Biancheri, R., & Filocamo, M. (2008). Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles. Human Mutation, 29(11). https://doi.org/10.1002/humu.20851

Grossi, S, Regis, S , Rosano, C , Corsolini, F, Uziel, G, Sessa, M, Di Rocco, M, Parenti, G, Deodato, F, Leuzzi, V, Biancheri, R & Filocamo, M 2008, 'Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles', Human Mutation, vol. 29, no. 11. https://doi.org/10.1002/humu.20851

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title = "Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles",

abstract = "Metachromatic leukodystrophy (MLD), the demyelinating disorder resulting from impaired sulfatide catabolism, is caused by allelic mutations of the Arylsulfatase A (ARSA) locus except for extremely rare cases of Saposin-B (Sap-B) deficiency. We characterized twenty-one unrelated Italian patients among which seventeen were due to ARSA activity deficiency and 4 others resulted from Saposin-B defect. Overall, we found 20 different mutant ARSA alleles and 2 different Sap-B alleles. The eleven new ARSA alleles (c.53C>A; c.88G>C; c.372G>A; c.409_411delCCC; c.634G>C; [c.650G>A;c.1108C>T]; c.845A>G; c.906G>C; c.919G>T; c.1102-3C>G; c.1126T>A) were functionally characterized and the novel amino acid changes were also modelled into the three-dimensional structure. The present study is aimed at providing a broader picture of the molecular basis of MLD in the Italian population. It also emphasizes the importance of a comprehensive evaluation in MLD diagnosis including biochemical, enzymatic and molecular investigations.",

keywords = "ARSA, Arylsulfatase A, Demyelinating disorder, Functional study, Metachromatic leukodystrophy, MLD, Modelling, Molecular analysis, Saposin-B",

author = "Serena Grossi and Stefano Regis and Camillo Rosano and Fabio Corsolini and Graziella Uziel and Maria Sessa and {Di Rocco}, Maja and Giancarlo Parenti and Federica Deodato and Vincenzo Leuzzi and Roberta Biancheri and Mirella Filocamo",

year = "2008",

month = nov,

doi = "10.1002/humu.20851",

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T1 - Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy

T2 - Identification and functional characterization of 11 novel ARSA alleles

AU - Grossi, Serena

AU - Regis, Stefano

AU - Rosano, Camillo

AU - Corsolini, Fabio

AU - Uziel, Graziella

AU - Sessa, Maria

AU - Di Rocco, Maja

AU - Parenti, Giancarlo

AU - Deodato, Federica

AU - Leuzzi, Vincenzo

AU - Biancheri, Roberta

AU - Filocamo, Mirella

PY - 2008/11

Y1 - 2008/11

N2 - Metachromatic leukodystrophy (MLD), the demyelinating disorder resulting from impaired sulfatide catabolism, is caused by allelic mutations of the Arylsulfatase A (ARSA) locus except for extremely rare cases of Saposin-B (Sap-B) deficiency. We characterized twenty-one unrelated Italian patients among which seventeen were due to ARSA activity deficiency and 4 others resulted from Saposin-B defect. Overall, we found 20 different mutant ARSA alleles and 2 different Sap-B alleles. The eleven new ARSA alleles (c.53C>A; c.88G>C; c.372G>A; c.409_411delCCC; c.634G>C; [c.650G>A;c.1108C>T]; c.845A>G; c.906G>C; c.919G>T; c.1102-3C>G; c.1126T>A) were functionally characterized and the novel amino acid changes were also modelled into the three-dimensional structure. The present study is aimed at providing a broader picture of the molecular basis of MLD in the Italian population. It also emphasizes the importance of a comprehensive evaluation in MLD diagnosis including biochemical, enzymatic and molecular investigations.

AB - Metachromatic leukodystrophy (MLD), the demyelinating disorder resulting from impaired sulfatide catabolism, is caused by allelic mutations of the Arylsulfatase A (ARSA) locus except for extremely rare cases of Saposin-B (Sap-B) deficiency. We characterized twenty-one unrelated Italian patients among which seventeen were due to ARSA activity deficiency and 4 others resulted from Saposin-B defect. Overall, we found 20 different mutant ARSA alleles and 2 different Sap-B alleles. The eleven new ARSA alleles (c.53C>A; c.88G>C; c.372G>A; c.409_411delCCC; c.634G>C; [c.650G>A;c.1108C>T]; c.845A>G; c.906G>C; c.919G>T; c.1102-3C>G; c.1126T>A) were functionally characterized and the novel amino acid changes were also modelled into the three-dimensional structure. The present study is aimed at providing a broader picture of the molecular basis of MLD in the Italian population. It also emphasizes the importance of a comprehensive evaluation in MLD diagnosis including biochemical, enzymatic and molecular investigations.

KW - ARSA

KW - Arylsulfatase A

KW - Demyelinating disorder

KW - Functional study

KW - Metachromatic leukodystrophy

KW - MLD

KW - Modelling

KW - Molecular analysis

KW - Saposin-B

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Molecular analysis of ARSA and PSAP genes in twenty-one italian patients with metachromatic leukodystrophy: Identification and functional characterization of 11 novel ARSA alleles

Abstract

Keywords

ASJC Scopus subject areas

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