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A partial deletion of the aspartoacylase gene is the cause of Canavan disease in a family from Mexico
  2. SIMA SAM,
  1. Department of Pediatrics, University of Illinois at Chicago, 840 S Wood Street, Room 211CSN (MC 857), Chicago, IL 60612, USA
  1. Dr Quan, quanf{at}

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Editor—Canavan disease (McKusick No 271900) is an autosomal recessive disorder characterised by spongy degeneration of the brain. This disorder is most prevalent in people of Ashkenazi Jewish descent but has been observed in other ethnic groups. Patients have severe mental retardation, poor head control, macrocephaly, and seizures. Canavan disease is caused by the accumulation of N-acetylaspartic acid (NAA) in the brain as the result of a deficiency of aspartoacylase (ASPA) (EC activity.1

The human ASPA gene has been mapped to chromosome 17p13. The gene spans a distance of approximately 30 kb and is organised into six exons.2 Previously described mutations in the ASPA gene include single nucleotide changes leading to missense, nonsense, and exon skipping mutations and frameshift mutations caused by the insertion or deletion of a small number (1-4 bp) of nucleotides.3 In Ashkenazi Jewish patients, the E285, Y231X, and 433-2(A to G) mutations account for approximately 82.9%, 14.8%, and 1.1% of disease alleles respectively. The predominant mutation in non-Jewish patients is the A305E mutation, which accounts for approximately 60% of non-Jewish Canavan disease mutations.4 Surprisingly, large deletions involving the ASPA gene have not yet been described. Here, we report the first instance of a partial deletion of the ASPA gene in Canavan disease. Two affected children in a family from Mexico were homozygous for a 190 kb deletion. The parents of the affected sibs were second cousins once removed. There was no other family history of Canavan disease or other neurodegenerative disorder.

Testing of the affected children for the common Jewish and non-Jewish Canavan disease mutations was negative. Preliminary Southern blot experiments using an ASPA cDNA suggested that the affected children were …

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