HLA-identified donors are the best source of allogeneic hematopoietic stem cell transplants, and are available in approximately 40% of cases. If no HLA-identical core family member is found, an extended family search may be performed. The aim of the study was to summarize the 10-year (1990-1999) experience of our tertiary care center with extended family donor search. During this period, 356 patients and 2659 of their family members were tissue-typed; 239 patients were Jewish (67%) and 117 were Arabic (33%). An HLA-identical core-family donor was identified for 168 patients (47%): 95 Jewish (40%) and 73 Arabic (62%) (p < 0.0001); 49 patients (14%) had more than one potential donor. An extended family search (grandmother/grandfather, aunts, uncles, etc.) was performed in 38 of the remaining families, which were found to be consanguineous: five Jewish and 33 Arabic. One HLA match was found in the Jewish families (20%) and 21 in the Arabic families (64%). The odds ratio for an Arabic patient to find a donor in the extended family search was 8.75, as opposed to a Jewish patient. Overall, HLA-matched donors were found by core and extended family search for 53% of the patients. The rate for Arabic patients was 80% and for Jewish patients, 40% (p < 0.001). This difference may be explained by the greater number of siblings and higher rate of consanguinity in the Arabic population. In conclusion, an extended family search for potential HLA-matched donors is worthwhile, especially in distinct ethnic populations with high consanguinity, such as Israeli Arabs.
In order to investigate the sub-typing of the B5 antigen in Israeli (Jewish and Arabic) patients with Behçet's disease (BD) allele-specific genotyping of B51 and B52 alleles was performed in Israeli BD patients and healthy controls. Among the HLA-B51-positive BD patients, B*5101 was found to be the predominant allele, identified in 62% of all BD patients and 78% of Jewish BD patients. HLA-B*5101 was also the predominant allele in HLA-B51-positive healthy controls. HLA-B*5108 and B*5104 alleles were identified in 23% and 15% of B51-positive BD patients, respectively. The HLA-B*5201 allele was identified in all HLA-B52-positive patients and controls. Our study suggests that both HLA-B*5101 and HLA-B*5201 are the dominant alleles of HLA-B5 in Israeli BD patients.
Gaucher disease (GD), caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GBA), is the most common human glycolipid storage disease. The incidence of the disease is particularly high in the Ashkenazi Jewish population, with a carrier frequency of 0.068. The 1226A-->G and 84GG mutations are the two predominant disease-causing alleles. We investigated the association of various mutations in the GBA gene with different alleles of a highly polymorphic site in the adjacent pyruvate kinase (PKLR) gene. Ninety-seven unrelated type I GD patients of various genotypes were studied to determine their genotype for the PKLR gene trinucleotide repeat polymorphism. One hundred out of 104 (96%) alleles carrying the 1226G mutation also carried the A1 allele of the PKLR gene, which is present in only 6.7% of the control population. The calculated linkage disequilibrium between 1226G and the A1 allele of the PKLR gene is 0.957. Mutation 84GG was found to be uniquely associated with the PKLR A6 allele, with a linkage disequilibrium of 1.00. The association of several less frequent GD mutations with PKLR alleles was also studied. These results support the hypothesis that the 1226G and 84GG mutations in the Ashkenazi Jewish population each originated in a single founder. Further studies of the association of the 1226G and 84GG mutations with PKLR alleles in European non-Jewish GD patients could help in the study of the chronological order of these mutations and may shed light on the history of the Ashkenazi Jews in the past two millennia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.