|Tania N Masmas1*, Marianne Ifversen1, Jakob Ek2, Lone Schejbel3, Hanne V Marquart3, Klaus Müller1, Carsten Heilmann1, Susanne Kjaergaard2 and Maria Kirchhoff2|
|1 Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark|
|2 Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark|
|3 Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark|
|Corresponding Author :||Tania Nicole Masmas
Department of Pediatrics and Adolescent Medicine
Rigshospitalet, Copenhagen University Hospital
Blegdamsvej 9, 2100 Copenhagen, Denmark
Tel: 0045 4158 5010
E-mail: [email protected]
|Received: January 10, 2014; Accepted: March 24, 2014; Published: March 31, 2014|
|Citation: Masmas TN, Ifversen M, Ek J, Schejbel L, Marquart HV, et al. (2014) Application of aCGH Analysis in Patients with Primary Immunodeficiency of Unknown Genetic Origin – Identification of Atypical SAP Deficiency and Coronin-1a Deficiency. J Clin Cell Immunol 5:201. doi:10.4172/2155-9899.1000201|
|Copyright: © 2014 Masmas TN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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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.
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