Canavan disease: Mutations among Jewish and non-Jewish patients

Rajinder Kaul, Guang P. Gao, Maria Aloya, Kuppareddi Balamurugan, Arlene Petrosky, Kimberlee Michals, Reuben Matalon

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase (ASPA). Sixty-four probands were analyzed for mutations in the ASPA gene. Three point mutations-693C→A, 854A→C, and 914C→A-were identified in the coding sequence. The 693C→A and 914C→A base changes, resulting in nonsense tyr231→ter and missense ala305→glu mutations, respectively, lead to complete loss of ASPA activity in in vitro expression studies. The 854A→C transversion converted glu to ala in codon 285. The glu285→ala mutant ASPA has 2.5% of the activity expressed by the wild-type enzyme. A fourth mutation, 433 -2(A→G) transition, was identified at the splice-acceptor site in intron 2. The splice-site mutation would lead to skipping of exon 3, accompanied by a frameshift, and thus would produce aberrant ASPA. Of the 128 unrelated Canavan chromosomes analyzed, 88 were from probands of Ashkenazi Jewish descent. The glu285→ala mutation was predominant (82.9%) in this population, followed by the tyr231→ter (14.8%) and 433 -2(A→G) (1.1%) mutations. The three mutations account for 98.8% of the Canavan chromosomes of Ashkenazi Jewish origin. The ala305→glu mutation was found exclusively in non-Jewish probands of European descent and constituted 60% of the 40 mutant chromosomes. Predominant occurrence of certain mutations among Ashkenazi Jewish and non-Jewish patients with Canavan disease would suggest a founding-father effect in propagation of these mutant chromosomes.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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