Multiple mutations are responsible for the high frequency of 2 lysosomal storage diseases in a small geographic area

Late infantile metachromatic leukodystrophy is relatively frequent among Arabs in the Galilee. The disease has been diagnosed in 7 Christian and Muslem unrelated families originating from 7 villages in a 20x20 kms area. Molecular analysis of the aryl sulfatase A gene revealed that the disease is caused in these 7 families by 5 different mutations. In each case the patients were homozygous for one of the mutations. Four of the mutations are unique up to now while the other mutation has been reported in Australian patients originating from Lebanon (T274M). This mutation may have been introduced to the Galilee from Lebanon. Comparable observations have been reported by Bach who demonstrated that the high incidence of another lysosmal storage disease, Hurler syndrome, among Arabs and Druses originating from the same region of the Galilee is due to 3 different novel mutations. The Arab population in the lower Galilee is very inbred and large families are very frequent. In this type of population it is expected that relatively soon (3 generations) after a first mutation event the first affected individual will be born. The possible causes for the increase frequency of new mutations in the region are under investigation. We will trymore » to determine whether it may be a general phenomenon which affects various genes or whether it is unique to lysosomal storage disorders.« less