THE MOLECULAR-BASIS OF CANAVAN (ASPARTOACYLASE DEFICIENCY) DISEASE INEUROPEAN NON-JEWISH PATIENTS

SHAAG A ANIKSTER Y CHRISTENSEN E GLUSTEIN JZ FOIS A MICHELAKAKIS H NIGRO F PRONICKA E RIBES A ZABOT MT ELPELEG ON

A. Shaag et al., THE MOLECULAR-BASIS OF CANAVAN (ASPARTOACYLASE DEFICIENCY) DISEASE INEUROPEAN NON-JEWISH PATIENTS, American journal of human genetics, 57(3), 1995, pp. 572-580

19

INGLESE

Article

Genetics & Heredity

American journal of human genetics → ACNP

0002-9297

57

3

1995

572 - 580

ISI

0002-9297(1995)57:3<572:TMOC(D>2.0.ZU;2-V

Canavan disease is an infantile neurodegenerative disease that is due to aspartoacylase deficiency. The disease has been reported mainly in Ashkenazi Jews but also occurs in other ethnic groups. Determination o f enzymatic activity for carrier detection and prenatal diagnosis is c onsidered unreliable. In the present study, nine mutations were found in the aspartoacylase gene of 19 non-Jewish patients. These included f our point mutations (A305E [39.5% of the mutated alleles], C218X [15.8 %], F295S [2.6%], and G274R [5.3%]); four deletion mutations (827 delG T [5.3%], 870de14 [2.6%], 566del7 [2.6%], and 527del6 [2.6%]); and one exon skip (527 del108 [5.3%]). The A305E mutation is panEuropean and probably the most ancient mutation, identified in patients of Greek, P olish, Danish, French, Spanish, Italian, and British origin. In contra st, the G274R and 527 del108 mutations were found only in patients of Turkish origin, and the C218X mutation was identified only in patients of Gypsy origin. Homozygosity for the A305E mutation was identified i n patients with both the severe and the mild forms of Canavan disease. Mutations were identified in 31 of the 38 alleles, resulting in an ov erall detection rate of 81.6%. All nine mutations identified in non-Je wish patients reside in exons 4-6 of the aspartoacylase gene. The resu lts would enable accurate genetic counseling in the families of 13 (68 .4%) of 19 patients, in whom two mutations were identified in the aspa rtoacylase cDNA.