- Email: [email protected]
Epidermolysis Bullosa Care in Israel
Epidermolysis Bullosa C a re i n I s r a e l Eli Sprecher, MD, PhD KEYWORDS Epidermolysis bullosa Keratin Blisters Epidermis Intermediate filaments Mutation
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.1 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.2 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.2 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.2 Unfortunately, no official survey on EB in Israel has been performed, so the true prevalence of the disease in this region remains unknown.
R125 mutations are rare in the Israeli populations.2,3 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.2,4 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,
Box 1 Laboratories offering molecular testing for EB in Israel and the Palestinian authority Laboratory of Molecular Dermatology Director: Dr Ofer Sarig Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, Tel Aviv 64239, Israel Telephone: 1972 3 697 3720; e-mail address: [email protected] Hereditary Research Laboratory
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.
Director: Dr Moien Kanaan Life Science Department, Bethlehem University, POB 9 or Jerusalem POB 54866 Telephone: 1972 2 274 4233; e-mail address: [email protected]
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel E-mail address: [email protected] Dermatol Clin 28 (2010) 429–430 doi:10.1016/j.det.2010.02.019 0733-8635/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.
derm.theclinics.com
MOLECULAR FEATURES OF EB IN ISRAEL
430
Sprecher resulting in significant cost and time saving Box 1.5
REFERENCES 1. Zlotogora J. Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am J Med Genet 1997;68(4):472–5. 2. Abu Sa’d J, Indelman M, Pfendner E, et al. Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern population. J Invest Dermatol 2006;126(4):777–81.
3. Ciubotaru D, Bergman R, Baty D, et al. Epidermolysis bullosa simplex in Israel: clinical and genetic features. Arch Dermatol 2003;139(4):498–505. 4. Nakano A, Lestringant GG, Paperna T, et al. Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families. J Am Acad Dermatol 2002;46(4):510–6. 5. Mizrachi-Koren M, Shemer S, Morgan M, et al. Homozygosity mapping as a screening tool for the molecular diagnosis of hereditary skin diseases in consanguineous populations. J Am Acad Dermatol 2006;55(3):393–401.
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.1 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.2 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.2 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.2 Unfortunately, no official survey on EB in Israel has been performed, so the true prevalence of the disease in this region remains unknown.
R125 mutations are rare in the Israeli populations.2,3 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.2,4 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,
Box 1 Laboratories offering molecular testing for EB in Israel and the Palestinian authority Laboratory of Molecular Dermatology Director: Dr Ofer Sarig Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, Tel Aviv 64239, Israel Telephone: 1972 3 697 3720; e-mail address: [email protected] Hereditary Research Laboratory
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.
Director: Dr Moien Kanaan Life Science Department, Bethlehem University, POB 9 or Jerusalem POB 54866 Telephone: 1972 2 274 4233; e-mail address: [email protected]
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel E-mail address: [email protected] Dermatol Clin 28 (2010) 429–430 doi:10.1016/j.det.2010.02.019 0733-8635/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.
derm.theclinics.com
MOLECULAR FEATURES OF EB IN ISRAEL
430
Sprecher resulting in significant cost and time saving Box 1.5
REFERENCES 1. Zlotogora J. Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am J Med Genet 1997;68(4):472–5. 2. Abu Sa’d J, Indelman M, Pfendner E, et al. Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern population. J Invest Dermatol 2006;126(4):777–81.
3. Ciubotaru D, Bergman R, Baty D, et al. Epidermolysis bullosa simplex in Israel: clinical and genetic features. Arch Dermatol 2003;139(4):498–505. 4. Nakano A, Lestringant GG, Paperna T, et al. Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families. J Am Acad Dermatol 2002;46(4):510–6. 5. Mizrachi-Koren M, Shemer S, Morgan M, et al. Homozygosity mapping as a screening tool for the molecular diagnosis of hereditary skin diseases in consanguineous populations. J Am Acad Dermatol 2006;55(3):393–401.