A null HLA‐A*68 allele in a bone marrow donor

Abstract

The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non-sense codon in the same exon.

No HLA-A gene detectable on one of the haplotypes in a caucasian family

“…In A*2436N a two-nucleotide deletion in exon 2 resulted in an immediate premature stop codon [11]. In both A*2440N, with a deletion of two nucleotides in exon 4, and A*6811N, with a deletion of one nucleotide in exon 1, the deletion resulted in a reading frame shift, causing a premature stop codon [1,12].…”

“…The lack of expression can be different in origin: either point mutations giving rise to premature stop codons [4, 8 -10], deletions or insertions leading to a frame shift and a premature termination [4,5,[11][12][13][14], deletions causing a structural defect in the molecule [15], mutations affecting transcription [2,7], and RNA splicing [4 -6, 16]; or hypermethylation leading to gene inactivation [3].…”

Exon 5 Encoding the Transmembrane Region of HLA-A Contains a Transitional Region for the Induction of Nonsense-Mediated mRNA Decay

“…These null alleles have substitutions, insertions, or deletions that prevent or reduce the expression of an HLA class I molecule at the cell surface. To date some 25 HLA class I null alleles have been described (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). HLA class II null alleles are also known, but to a lesser extent than for class I (22)(23)(24)(25)(26)(27)(28)(29).…”

HLA-Cw*0409N is associated with HLA-A*2301 and HLA-B*4403-carrying haplotypes

“…The total number of HLA-B*4403 haplotypes associated with HLA-A*2301 in all three panels was therefore 21/61 (34%). Two haplotypes from the third panel carried HLACw*0409N, one with HLA-A*2301 and one with HLA-A*0201.In summary, the total number of HLA-B*4403-positive haplotypes that carried HLA-Cw*0409N was8 of 61 (13%). Of all 40 haplotypes containing both HLA-B*4403 and HLA-Cw*04, 32 (80%) carried HLACw*0401, although 8 (20%) carried HLA-Cw*0409N.…”

“…These alleles are detected by molecular but not serologic methods. Several null alleles have been reported in the human leukocyte antigen (HLA) class I molecules [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. The first HLA-Cw4 null allele was reported [15,16] and named Cw*0409N by the WHO Nomenclature Committee.…”