The Israeli population is characterized by unique demographic features including high genetic homogeneity within many closed communities. As a consequence the molecular epidemiology of epidermolysis bullosa differs markedly in this country and surrounding areas from that reported in the Western world.
Epidemiology of epidermolysis bullosa in Israel
The Israeli population is composed of many ethnic communities, which have been living for centuries in a state of genetic isolation, one community relative to the other community. As a consequence, these communities, where consanguineous marriages are traditionally common, are characterized by genetic homogeneity, which in turn is associated with an excess prevalence of recessive disorders. Thus, it is not entirely surprising that, although autosomal recessive epidermolysis bullosa simplex (EBS) is exceedingly rare worldwide, it accounts in Israel for approximately one-third of all EBS cases. This in turn has significant implications for the genetic counseling of families at risk for EBS. Similarly, in contrast with the situation in Europe and in the United States, dominant forms of dystrophic epidermolysis bullosa (EB) are more rare in Israel than recessive forms of the disease. Finally, the same demographic features may also underlie the fact that, although autosomal recessive junctional EB accounts in Western populations for less than 5% of the total number of EB cases, in Israel it comprises more than 25% of the cases. Unfortunately, no official survey on EB in Israel has been performed, so the true prevalence of the disease in this region remains unknown.
Molecular features of EB in Israel
Several recurrent molecular features identified in Western populations are absent in Israeli patients with EB. For example, most cases of EBS result from mutations affecting KRT14 R125 residue. R125 mutations are rare in the Israeli populations. Similarly, most cases of junctional EB are due to a few specific mutations in LAMB3 . Not only are these mutations rare in the Israeli and Middle Eastern populations but also the proportion of cases resulting from mutations in LAMB3 as compared with LAMA3 and LAMC2 is different from in Western countries. These peculiarities most certainly relate to the demographic features characteristic of Middle Eastern populations with a high coefficient of inbreeding ensuring the propagation of rare genetic variants within closed communities.
Similarly, most recessive forms of EB are due to homozygous mutations. This in turn can be exploited to screen affected families using homozygosity mapping, before formal mutation analysis, resulting in significant cost and time saving Box 1 .