Journal Article

An HLA haplotype with a deletion at the HLA-A locus: A case report

Riva, M, Rovelli, A, Mascaretti, L, Sala, E, Poli, F, Crosti, F, Longhi, E, Frison, S, Balduzzi, A, Corti, P, Crespiatico, L

2005

Overview

We report an HLA haplotype with a deletion at the HLA-A locus in a 7 year old patient of Caucasian origin affected by Late Onset Globoid Cell Leukodystrophy, a rare autosomic recessive disease due to mutations in the galactosylceramidase gene localized on chromosome 14. Allogeneic bone marrow transplantation (BMT) in selected cases has proved successful. Materials and methods: HLA typing was performed with lymphocytotoxicity, low and high resolution PCR-SSP and SBT. Microsatellites close to the HLA-A locus (D6S2700, D6S2705, D6S265, D6S510, RF, D6S276) and the HFE gene were determined in order to assess the extent of deletion. Results: the patient (HLA-A1) inherited HLA-A1 from her father (HLA-A1, 24) and apparently no HLA-A specificity from her mother (HLA-A30). High resolution typing could not demonstrate any known HLA-A null allele. SBT for the patient only identified HLA-A*010101. The most probable hypothesis seemed a deletion at the HLA-A locus. All microsatellites analysed showed no deletion suggesting that the genomic DNA loss was closer to the HLA-A locus, between the D6S510 and the RF microsatellites. BMT was carried out with a donor bearing a single DQB1*mismatch; although engraftment was successful and no GvHD evidenced, disease progression could not be halted. Conclusion: an inherited haplotype carrying a small deletion at the HLA-A locus was described. Further investigation will include a karyotype analysis.