Tay-Sachs disease in Moroccan Jews: Deletion of a phenylalanine in the α-subunit of β-hexosaminidase

Tay-Sachs disease is an inherited lysosomal storage disorder caused by defects in the β-hexosaminidase α-subunit gene. The carrier frequency for Tay-Sachs disease is significantly elevated in both the Ashkenazi Jewish and Moroccan Jewish populations but not in other Jewish groups. We have found that the mutations underlying Tay-Sachs disease in Ashkenazi and Moroccan Jews are different. Analysis of a Moroccan Jewish Tay-Sachs patient has revealed an in-frame deletion (ΔF) of one of the two adjacent phenylalanine codons that are present at positions 304 and 305 in the α-subunit sequence. The mutation impairs the subunit assembly of β-hexosaminidase A, resulting in an absence of enzyme activity. The Moroccan patient was found also to carry, in the other α-subunit allele, a different, and as yet unidentified, mutation which causes a deficit of mRNA. Analysis of obligate carriers from six unrelated Moroccan Jewish families showed that three harbor the ΔF mutation, raising the possibility that this defect may be a prevalent mutation in this ethnic group.