Jornal de Imunologia Clínica e Celular
Acesso livre

Abstrato

Application of aCGH Analysis in Patients with Primary Immunodeficiency of Unknown Genetic Origin – Identification of Atypical SAP Deficiency and Coronin-1a Deficiency

Tania N Masmas, Marianne Ifversen, Jakob Ek, Lone Schejbel, Hanne V Marquart, Klaus Müller, Carsten Heilmann, Susanne Kjaergaard and Maria Kirchhoff

Objective: Patients with primary immunodeficiencies (PID) verified by clinical disease and standard immunological diagnostics but without a genetic diagnosis remain a challenge. Genetic diagnosis is important in order to plan follow-up and treatment possibilities including bone marrow transplantation and genetic counselling.
Methods: We used array comparative genomic hybridization (aCGH) analysis to investigate a cohort of pediatric patients with PID of unknown genetic origin in order to investigate the diagnostic yield of applying this technique to such patients and in an attempt to identify new possible genetic explanations for immunodeficiencies.
Results: Chromosomal imbalances were found in four of 14 investigated patients. In two cases a genetic diagnosis was established involving the SH2 domain-containing protein 1A gene (SH2D1A) and the Coronin-1a gene (CORO1A) causing atypical SLAM (signaling lymphocyte activation molecule)-associated protein (SAP) deficiency and Coronin-1a deficiency, respectively. Identification of the heterozygote deletion including the CORO1A gene by aCGH analysis led to sequencing of the other allele and identification of a novel point mutation. The clinical relevance of the deletions in the remaining two patients is not yet clarified but involves genes (the dedicator of cytokinesis 4 gene (DOCK4) and the protease, serine, 16 (thymus) gene (PRSS16) with suspected immunological functions.
Conclusion: Applying aCGH analysis in case of rare severe symptoms of immunodeficiency may be of great importance in order to establish a diagnosis and treat the patients appropriately. We identified a case of atypical SAP deficiency with no comparable cases in the literature, and a case of Coronin-1a deficiency of which only two families have previously been described.