Spectrum of Canavan mutations among Jewish and non-Jewish patients

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133427

Kaul, R K; Matalon, R; Gao, G P ^[1]

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1. Miami Childrens`s Hospital, FL (United States); and others

Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase (ASPA) and accumulation of N-acetylapartic acid in brain. The cDNA and the gene for ASPA has been isolated and localized to 17q13-ter. Single strand conformation polymorphism followed by DNA sequencing and/or restriction endonuclease digestion of PCR amplified genomic DNA and cDNA were used for identification of Canavan mutations. The effect of these mutations on ASPA activity was determined by in vitro expression studies. We have analyzed 158 Canavan chromosomes for mutations in ASPA gene. A total of 13 different mutations were identified in the ASPA gene. The distribution of these mutations among patients of different ethnic groups is unique. Of the 100 Jewish Canavan chromosomes, E285{yields}A missense mutation was predominant in 83%, followed by Y231{yields}X nonsense mutation in 13%. The A305{yields}E mutation in Jewish patients was found in 2 alleles; both of which were of non-Jewish origin. The two predominant Jewish mutations account for 96% of the mutant alleles in this ethnic group. Among the 52 non-Jewish chromosomes of European descent, A305{yields}E missense mutation was predominant in 46.15% alleles; whereas E285{yields}A and Y232{yields}X mutations each account for 3.8% mutant alleles. Six other mutations including missense and deletions were identified in non-Jewish patients of European descent. These mutations account for 21.15% mutant alleles, resulting in an overall detection of 75%. The 3 Arab patient were each homozygous for 3 different mutations that included 2 missense and one exon skipping mutation(s). The implication of these mutations is discussed in terms of their origin, carrier detection and epidemiology in the risk population and pre-natal diagnosis in informative families.

• OSTI ID: 133427
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DNA SEQUENCING
ENZYMES
EPIDEMIOLOGY
GENE MUTATIONS
GENES
GENETIC MAPPING
GENETIC VARIABILITY
HEREDITARY DISEASES
HUMAN CHROMOSOME 17
MINORITY GROUPS
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS