Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community

In the last 15 years, four patients With the infantile form of Sandhoff dis ease were diagnosed in four different families in Cyprus (population 703,00 0, birth rate 1.7%). Three of these cases came from the Christian Maronite community (less than 1% of the population) and one from the Creek community (84% of the population). This relatively large number of patients prompted us to initiate an epidemiological study in order to establish the frequenc y of the mutant allele in Cyprus. Carrier detection was initially based on the measurement of beta-hexosaminidase A and B in both leucocytes and serum . Using the enzyme test, 35 carriers were identified among 234 random Maron ite samples and 15 among 28 h Maronites with a family history of Sandhoff d isease, but only one carrier was found out of 115 random samples from the G reek community. in parallel to the biochemical screening. DNA studies were undertaken in one of I-he three Maronite patients and in a Greek: carrier r elated to the Greek patient. These studies resulted in the identification o f two novel mutations, a deletion of A at nt76 and a G to C transversion at position 5 of the 5'-splice site of intron 8, which have been published. W e subsequently screened the carriers detected in the biochemical study for these two mutations using PCR-based tests. Of 50 Maronite carriers examined , 42 were found to have the nt76 deletion. Eight Maronite samples, designat ed carriers from the biochemical results, were negative for both mutations. It is possible that these individuals were incorrectly classified as carri ers since their enzyme values are equivocal, although the presence of anoth er mutation has not been excluded. Two Greek Cypriot carriers and two oblig ate Lebanese carriers were negative for both mutations. We conclude that th ere is a high frequency of Sandhoff disease carriers in the Maronite commun ity of Cyprus, approximately I in 7, and that a single mutation predominate s in this population.