Case Report: Similar STR profiles in non-twin siblings complicating chimerism analysis after allogeneic hematopoietic...

Fanconi anemia (FA) is an inherited bone marrow (BM) failure syndrome for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option. Short tandem repeat (STR) profiling is the reference molecular method for post-transplant chimerism monitoring, but its analytical performance depends on the presence of informative allelic differences between donor and recipient. We report a 3-year-old boy with FA carrying a homozygous FANCA c.2778 + 1G > A variant who underwent allo-HSCT from a human leukocyte antigen (HLA)-matched non-twin sibling donor. Pre-transplant STR analysis using two independent multiplex systems (PowerPlex^® 16 and PowerPlex^® ESI 16 Fast) revealed near-complete donor-recipient genetic concordance, with only a single informative autosomal locus (D13S317) available for chimerism tracking. Despite this analytical limitation, the patient achieved neutrophil engraftment on day +13 and platelet engraftment with sustained trilineage recovery through day +1376 (approximately 3.75 years post-transplant). Serial post-transplant STR monitoring demonstrated absence of the recipient-specific allele at D13S317, consistent with full donor-derived hematopoiesis and corroborated by independent assay replication and the clinical engraftment course. To our knowledge, this is among the first reported cases of single-locus STR informativity complicating post-HSCT chimerism analysis in a pediatric FA patient from a consanguineous population. In populations with high consanguinity, this case demonstrates a rare but actionable limitation of standard STR-based chimerism monitoring in non-twin siblings. It underscores the value of pre-transplant verification of donor-recipient STR informativity, predefined escalation to high-resolution alternatives such as digital PCR or next-generation sequencing-based chimerism analysis when fewer than two informative loci are identified, and cautious reporting language when molecular informativity is constrained.