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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
Author(s) -
Grossi Serena,
Regis Stefano,
Rosano Camillo,
Corsolini Fabio,
Uziel Graziella,
Sessa Maria,
Di Rocco Maja,
Parenti Giancarlo,
Deodato Federica,
Leuzzi Vincenzo,
Biancheri Roberta,
Filocamo Mirella
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20851
Subject(s) - metachromatic leukodystrophy , arylsulfatase a , biology , allele , genetics , locus (genetics) , gene , leukodystrophy , genotype , microbiology and biotechnology , biochemistry , medicine , disease
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. © 2008 Wiley‐Liss, Inc.