A new HLA-A1 mutation: a novel, null variant allele.
From an unusually informative family of 8 with near identical parental haplotypes (a and c), which differed by a single nucleotide substitution, we identified a new HLA-A1 null variant. While serologic antigen typing initially showed a "blank" allele in maternal haplotype "c" and 2 male offspring, more sophisticated DNA molecular HLA typing subsequently revealed the presence of a novel HLA-A0101 allele. Sequence-based typing showed a point mutation consisting of a nucleotide substitution of a cytosine for a guanine at nucleotide 215 yielding an amino acid change of arginine to proline at codon 48 in exon 2 (R48P). The impact on the HLA and immunogenetics laboratory is the need to not assume that all blanks are homozygous, as well as the need for the availability of high-resolution DNA molecular typing to clarify new alleles and to detect HLA-A null variants.
Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
John Bernard
JB
Henry
Charlene A
CA
Hubbell
Mary C
MC
Davis
Marcelo A
MA
Fernandez-Vina
Edmond J
EJ
Yunis
Antony E
AE
Shrimpton
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015788:HLA-A1 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D015788:HLA-A1 Antigen