An unusual arylsulfatase A pseudodeficiency allele carrying a splice site mutation in a metachromatic leukodystrophy patient.
A late infantile metachromatic leukodystrophy patient was found to be heterozygous for the arylsulfatase A (ARSA) pseudodeficiency (pd) polyadenylation site variant ((*)96A>G) in the absence of the commonly associated N-glycosylation site variant (N350S). ARSA alleles were sequenced and the genotype completely defined. Six sequence variations were identified, among which two resulted as severe disease-causing mutations, both leading to the loss of the reading frame: a splice acceptor site mutation in intron 4 (849-1G>A), located on the (*)96A>G allele and a mononucleotide deletion (258delC) in exon 2, located on the other allele. The altered splicing caused by the 849-1G>A mutation was shown by in vitro expression of a recombinant gene containing the genomic region surrounding the mutation. Haplotype analysis of the unusual pd allele was performed in order to investigate its possible origin.
Regis
Stefano
S
Laboratorio di Diagnosi Pre e Postnatale di Malattie Metaboliche, Istituto G Gaslini, Largo G Gaslini 5, Genova 16147, Italy. stefanoregis@ospedale-gaslini.ge.it
Corsolini
Fabio
F
Ricci
Verena
V
Di Duca
Marco
M
Filocamo
Mirella
M
D000483:Alleles; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers; D005822:Genetic Vectors; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics*; D008969:Molecular Sequence Data; D012326:RNA Splicing
D017931:DNA Primers; D002553:Cerebroside-Sulfatase