Canavan disease: Mutations among Jewish and non-Jewish patients

Journal Article · Fri Jul 01 04:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:6789782

Kaul, R; Gao, G P; Aloya, M; Balamurugan, K; Petrosky, A; Michals, K; Matalon, R ^[1]

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1. Miami Children's Hospital, FL (United States)

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[yields]A, 854[yields]C, and 914C[yields]A-were identified in the coding sequence. The 693C[yields]A and 914C[yields]A base changes, resulting in nonsense tyr231[yields]ter and missense ala305[yields]glu mutations, respectively, lead to complete loss of ASPA activity in in vitro expression studies. The 854A[yields]C transversion converted glu to ala in codon 285. The glu285[yields]ala mutant ASPA has 2.5% of the activity expressed by the wild-type enzyme. A fourth mutation, 433 -2(A[yields]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[yields]ala mutation was predominant (82.9%) in this population, followed by the tyr231[yields]ter (14.8%) and 433 -2(A[yields]G) (1.1%) mutations. The three mutations account for 98.8% of the Canavan chromosomes of Ashkenazi Jewish origin. The ala305-[yields]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. 25 refs., 8 figs., 4 tabs.

• OSTI ID: 6789782
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 55:1; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ASPARTIC ACID
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CYCLASES
DISEASES
DNA SEQUENCING
ENZYMES
GENE MUTATIONS
HEREDITARY DISEASES
LYASES
MUTATIONS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS