Infantile Krabbe disease is a severe, fatal autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity. It is relatively common in two separate inbred communities in Israel. In the Druze community in Northern Israel and two Moslem Arab villages located near Jerusalem the incidence of Krabbe disease is about 1 in 100–150 live births. With our cloning of the GALC gene, mutation analysis of these populations was undertaken. The Moslem Arabs were homozygous for two mutations in the GALC gene; a T-to-C transition at cDNA position 1637 (counting from the A of the initiation codon), which is 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 1748, which changes the codon for isoleucine to one for serine. Expression studies confirmed the deleterious nature of these mutations. The development of a simple polymerase chain reaction (PCR) amplification and restriction enzyme digestion method to identify these alleles will lead to accurate carrier testing and improved genetic counseling for interested individuals in these communitie
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