– HLA Lab Director, King Hussein Cancer Center, Jordan
Body: Although many novel alleles have been discovered and registered in the last few years due to the advancement in sequencing including the use of next-generation sequencing (NGS), many rare alleles are waiting for reporting among different ethnicities and geographical regions. Herein we are comparing HLA-B*56:13 allele that was reported only in ten persons, all over the world, with persons from the Middle East and Northern Africa (MENA) region. RSSO typing using Luminex FLEXMAP 3D instrument, LABType™-XR reagents, and FUSION software 4.6, were used in typing of a family of seven siblings in a routine workup for allogeneic HSC transplant. In this family, six out of seven siblings had HLA-B*56:13. The expression of the HLA-B*56:13 allele was in the same combination with B*51:01 (i.e., B*51:01,56:13). The HLA-A, -B, and -DR typing for those persons were: A*01:01,32:01; B*51:01,56:13, and DRB1*04:01,11:04. These allele combinations had zero phased and unphased genotypes in NMDP database (i.e., HaploStats). By family haplotype analysis, the HLA-B*56:13 containing haplotype was A*32:01; B*56:13, and DRB1*11:04. This haplotype has zero match within the NMDP database (i.e., HaploStats) for B*56:13, compared to B*56:01 that was documented in many ethnicities including AFA, API, CAU, HIS, and NAM. The difference in amino acid sequence for B*56:01 vs. B*56:13, is located only in position #156 as “Leucine” in B*56:01:01:01 replaced by “Aspartate” in B*56:13. This mutation is lies in exon #3 at codon #156 at which “CTG” in B*56:01:01:01 replaced by “GAC” in B*56:13. Using Python for Population Genomics (https://pypop.org/), HLA-B*56:13 was first described in 2004 and has a frequency of 0.00000. Moreover in CIWD version 3.0.0, B*56:13 allele was only reported 10 times globally 5-times in Europeans (i.e., allele frequency: 4.19E-07), 2-times in Hispanic (i.e., allele frequency: 2.85E-06), and 3-times in Uknown ethnicities (i.e., allele frequency: 2.27E-06) ethnicities.
Conclusions: Although HLA-B*56:13 is considered a well-documented (WD) allele among the Europeans. Our data clearly shows, and for the first time, that this allele can be found in MENA populations mainly from Arab ethnicity. Although this is a rare allele but still can be counted for another ethnicity rather than the Europeans and Hispanic and should be considered, in the next CIWD version update, as WD allele among the MENA region.