Prevalance of Canavan disease heterozygotes in the New York Metropolitan Ashkenazi Jewish population
- New York Univ. Medical Center, NY (United States); and others
Canavan disease is a severe neurodegenerative disease that occurs most commonly in the Ashkenazi Jewish population. Previous studies have indicated the carrier frequency to be between 1/59 and 1/45. The disease, now recognized as a deficiency of aspartoacylase, is associated with the pathological finding of spongy degeneration of the brain. Patients are usually normal at birth, but by 2-4 mo they lose milestones and develop seizures, macrocephaly, and hypertonia. Death occurs in early childhood. With the availability of enzymatic testing, an increase in the incidence of newly diagnosed cases has been observed, suggesting that the frequency of the disorder may have been underestimated. In 1993, the cDNA for the aspartoacylase gene was cloned, and an A{yields}C transition at nucleotide 854 was identified in affected individuals. This represents a missense mutation from glutamine to alanine at amino acid residue 285 (E285A). This mutation was found in 73/88 Canavan disease-bearing chromosomes from Ashkenazi patients. In the same study, a C{yields}A transition at nucleotide 693, which results in the conversion from a tyrosine codon to terminator codon at position 231 (Y231X), was found in 13/88 chromosomes. Thus, these two mutations provide a detection rate >97% in this population. The aspartoacylase gene spans 23 kb of DNA and has been mapped to 17p13-ter by FISH. The gene consists of six coding exons. The E285A mutation is located in exon 6 and results in the creation of a new EagI site, whereas the Y231X mutation is found in exon S and creates an MseI site. In this study we have determined the frequency of these two mutations from a panel of unaffected individuals who live in the New York metropolitan area. 9 refs., 1 tab.
- OSTI ID:
- 209921
- Journal Information:
- American Journal of Human Genetics, Vol. 57, Issue 5; Other Information: PBD: Nov 1995
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
HUMAN POPULATIONS
NERVOUS SYSTEM DISEASES
HEREDITARY DISEASES
MORTALITY
DISEASE INCIDENCE
GENES
DNA-CLONING
GENE MUTATIONS
GENETIC MAPPING
MUTATION FREQUENCY
DETECTION
HUMAN CHROMOSOME 17
NEW YORK
EXONS
ENZYMES
NUCLEOTIDES
AMINO ACIDS
CODONS
DNA HYBRIDIZATION
FLUORESCENCE