2 DIFFERENT MUTATIONS ARE RESPONSIBLE FOR KRABBE DISEASE IN THE DRUZEAND MOSLEM-ARAB POPULATIONS IN ISRAEL

Infantile Krabbe disease is a severe, fatal autosomal recessive disord er resulting from the deficiency of galactocerebrosidase (GALC) activi ty. It is relatively common in two separate inbred communities in Isra el. In the Druze community in Northern Israel and two Moslem Arab vill ages located near Jerusalem the incidence of Krabbe disease is about 1 in 100-150 live births. With our cloning of the GALC gene, mutation a nalysis of these populations was undertaken. The Moslem Arabs were hom ozygous for two mutations in the GALC gene; a T-to-C transition at cDN A position 1637 (counting from the A of the initiation codon), which i s considered a polymorphism, and a G-to-A transition at position 1582, which changes the codon for aspartic acid to one for asparagine. The Druze patients are homozygous for a T-to-G transversion at position 17 48, which changes the codon for isoleucine to one for serine. Expressi on studies confirmed the deleterious nature of these mutations. The de velopment of a simple polymerase chain reaction (PCR) amplification an d restriction enzyme digestion method to identify these alleles will l ead to accurate carrier testing and improved genetic counseling for in terested individuals in these communities.