Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease

Journal Article · Mon Jul 01 04:00:00 EDT 1996 · American Journal of Human Genetics

OSTI ID:443740

Kaul, R; Gao, G P; Matalon, R; Aloya, M ^[1]

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

Canavan disease is inherited as an autosomal recessive trait that is caused by the deficiency of aspartoacylase (ASPA). The majority of patients with Canavan disease are from an Ashkenazi Jewish background. Mutations in ASPA that lead to loss of enzymatic activity have been identified, and E285A and Y231X are the two predominant mutations that account for 97% of the mutant chromosomes in Ashkenzai Jewish patients. The current study was aimed at finding the molecular basis of Canavan disease in 25 independent patients of non-Jewish background. Eight novel and three previously characterized mutations accounted for 80% (40/50) of mutant chromosomes. The A305E missense mutation accounted for 48% (24/50) of mutant chromosomes in patients of western European descent, while the two predominant Jewish mutations each accounted for a single mutant chromosome. The eight novel mutations identified included 1- and 4-bp deletions (32 {Delta}T and 876 {Delta}AGAA, respectively) and I16T, G27R, D114E, G123E, C152Y, and R168C missense mutations. The homozygous 32 {Delta}T deletion was identified in the only known patient of African-American origin with Canavan disease. The heterozygosity for 876 {Delta}AGAA mutation was identified in three independent patients from England. Six single-base changes leading to missense mutations were identified in patients from Turkey (D114E, R168C), The Netherlands (I16T), Germany (G27R), Ireland (C152Y), and Canada (G123E). A PCR-based protocol is described that was used to introduce mutations in wild-type cDNA. In vitro expression of mutant cDNA clones demonstrated that all of these mutations led to a deficiency of ASPA and should therefore result in Canavan disease. 16 refs., 2 figs., 4 tabs.

• OSTI ID: 443740
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 1 Vol. 59; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENE REGULATION
GENES
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOMES
HUMAN POPULATIONS
METABOLIC DISEASES
MUTATION FREQUENCY
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS