Apparent maternal exclusion explained by a MICA deletion

A 31-year-old male undergoing evaluation for an allogeneic stem cell transplant exhibited a complete mismatch at the MICA locus compared to his biological mother. The recipient was homozygous MICA*008:04, while the mother was homozygous MICA*002:01. Sample mix-up was ruled out and we sought an alternative explanation. Upon investigation of MICA and HLA-B allele linkage, multiple studies reported an association of a MICA deletion (MICAdel) with HLA-B*48. Interestingly, the patient and his mother both typed as HLA-B*48:02. Furthermore, the patient and his mother each typed as MICB*09:01N. Copy number analysis confirmed a single copy of MICA in both samples, thus providing supporting evidence of a MICAdel in both subjects, and consistent with previously published data on the association of a MICAdel with HLA-B*48. What initially appeared to be a maternal exclusion based on a MICA mismatch was instead attributable to a hemizygous loss of MICA. This case highlights two important considerations: 1) evaluating other loci, not generally considered in most clinical matching algorithms can uncover interesting genetic anomalies usually described only in research settings, 2) The appreciation of such findings can lead to studies that explore the clinical impact of such an evolutionary change.