Short tandem repeats haplotyping of the HLA region in preimplantation HLA matching.
Recently, preimplantation genetic diagnosis (PGD) has been considered for several indications beyond its original purpose, not only to test embryos for genetic disease but also to select embryos for a nondisease trait, such as specific human leukocyte antigen (HLA) genotypes, related to immune compatibility with an existing affected child in need of a haematopoetic stem cell (HSC) transplant. We have optimized an indirect single-cell HLA typing protocol based on a multiplex fluorescent polymerase chain reaction (PCR) of short tandem repeat (STR) markers scattered throughout the HLA complex. The assay was clinically applied in 60 cycles from 45 couples. A conclusive HLA-matching diagnosis was achieved in 483/530 (91.1%) of the embryos tested. In total, 74 (15.3%) embryos revealed an HLA match with the affected siblings, 55 (11.4%) of which resulted unaffected and 46 (9.5%) have been transferred to the patients. Nine pregnancies were achieved, five healthy HLA-matched children have already been delivered and cord blood HSCs, were transplanted to three affected siblings, resulting in a successful haematopoietic reconstruction.
Fiorentino
Francesco
F
EmbryoGen - Center for Preimplantation Genetic Diagnosis, Rome, Italy. fiorentino@embryon.it
Kahraman
Semra
S
Karadayi
Hüseyin
H
Biricik
Anil
A
Sertyel
Semra
S
Karlikaya
Güvenc
G
Saglam
Yaman
Y
Podini
Daniele
D
Nuccitelli
Andrea
A
Baldi
Marina
M
D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D020080:Tandem Repeat Sequences
D006680:HLA Antigens