1. ¹Laboratorio di Diagnosi Pre e Postnatale di Malattie Metaboliche, Istituto G Gaslini, Largo G Gaslini 5, Genova 16147, Italy
2. ²Laboratorio di Fisiopatologia dell'Uremia, Istituto G Gaslini, Largo G Gaslini 5, Genova 16147, Italy

Correspondence: Dr S Regis and Dr M Filocamo, Laboratorio di Diagnosi Pre e Postnatale di Malattie Metaboliche, Istituto G. Gaslini, Largo G. Gaslini 5, Genova 16147, Italy. Tel: +39 010 5636792; Fax: +39 010 3776590; E-mail: stefanoregis@ospedale-gaslini.ge.it

Received 4 April 2003; Revised 22 July 2003; Accepted 9 September 2003; Published online 22 October 2003.

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.