A novel mutation in the HEXA gene specific to Tay-Sachs disease carriers of Jewish Iraqi origin

An increased frequency of carriers of 1:140, as defined by reduced hexosami nidase A (HexA) activity, was observed among Iraqi Jews participating in th e Tay-Sachs disease (TSD) carrier detection program. Prior to this finding, TSD among Jews had been restricted to those of Eastern European (Ashkenazi ) and Moroccan descent with carrier frequencies of 1:29 and 1:110 for Jews of Ashkenazi and Moroccan extraction, respectively. A general, pan-ethnic f requency of approximately 1:280 has been observed among other Jewish Israel i populations. Analysis of 48 DNA samples from Iraqi Jews suspected, by enz ymatic assay, to be carriers revealed a total of five mutations, one of whi ch was novel. In nine carriers (19%), a known mutation typical to either As hkenazi or Moroccan Jews was identified. Delta F304/ 305 was detected in fo ur individuals, and + 1278TATC in three. G269S and R170Q each appeared in a single person. The new mutation, G749T, resulting in a substitution of gly cine to valine at position 250 has been found in 19 of the DNA samples (40' %,). This mutation was not detected among 100 non-carrier, Iraqi Jews and 6 5 Ashkenazi enzymatically determined carriers. Aside from Ashkenazi and Mor occan Jews, a specific mutation in the HEXA gene has now also been identifi ed in Jews of Iraqi descent.