Abstract
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.
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Acknowledgements
The DNA samples used were obtained by the collection ‘Cell Line and DNA Bank from Patients affected by Genetic Disease’ (www.gaslini.org/labdppm.htm) supported by Italian Telethon grants (Project No. GTF02012).
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Regis, S., Corsolini, F., Ricci, V. et al. An unusual arylsulfatase A pseudodeficiency allele carrying a splice site mutation in a metachromatic leukodystrophy patient. Eur J Hum Genet 12, 150–154 (2004). https://doi.org/10.1038/sj.ejhg.5201100
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DOI: https://doi.org/10.1038/sj.ejhg.5201100
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