An unusual arylsulfatase A pseudodeficiency allele carrying a splice site mutation in a metachromatic leukodystrophy patient

Eur J Hum Genet. 2004 Feb;12(2):150-4. doi: 10.1038/sj.ejhg.5201100.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Base Sequence
  • Cerebroside-Sulfatase / genetics*
  • Cloning, Molecular
  • DNA Primers
  • Genetic Vectors
  • Humans
  • Leukodystrophy, Metachromatic / genetics*
  • Molecular Sequence Data
  • RNA Splicing*

Substances

  • DNA Primers
  • Cerebroside-Sulfatase

Associated data

  • RefSeq/NP_000478