Recurrent Homozygous DOCK8 Microdeletion Suggests a Founder Mutation in Two Unrelated Kaingang Children

Introduction Indigenous Kaingang communities of southern Brazil display a high burden of recessive disorders attributable to long-standing demographic isolation and high rate of consanguinity. We describe the clinical, immunological, and molecular profile of two unrelated Kaingang children with autosomal-recessive DOCK8 deficiency, a rare autosomal-recessive combined immunodeficiency in the general population. Methods A retrospective case review extracted clinical data, laboratory results, and genetic analyses from medical records. Results Case 1: Male, 5 years and 4 months, experienced recurrent cutaneous and fungal respiratory infections, severe atopic dermatitis, hepatosplenic involvement, microcytic anemia, and marked eosinophilia. Total IgE reached 19,391 IU/mL; CD4 counts were intermittently low and the dihydrorhodamine assay was abnormal. A multigene panel revealed a homozygous 299-bp deletion at 9p24.3 (g.334 155_334 454del), resulting in the loss of at least exon 11 of the DOCK8 gene. Case 2: Female, 5 years old, presented at 2 months of age with widespread eczematous lesions, multiple food and drug allergies, hyper-IgE, and persistent eosinophilia. A homozygous 1.5-kb deletion at 9p24.3 (g.333421_334903del) was identified by whole genome sequencing, resulting in the exon 11 loss in DOCK8 gene. She underwent allogeneic hematopoietic stem cell transplantation from a heterozygous sibling donor, achieving full donor chimerism and marked dermatological improvement, although IgE and eosinophilia remained elevated. The two deletions overlap by more than 90% and were found in children from neighboring, geographically isolated villages, strongly indicating a single ancestral breakpoint and a potential founder effect for DOCK8 deficiency in the Kaingang population. Conclusions The recurrence of an almost identical homozygous DOCK8 microdeletion in two indigenous Kaingang children from unrelated families points to a likely founder mutation in this ethnicity and could guide targeted carrier screening, genetic counseling, and early intervention strategies in this population.