Details

Autor(en) / Beteiligte

• van Schouwenburg, Pauline A
• Davenport, Emma E
• Kienzler, Anne-Kathrin
• Marwah, Ishita
• Wright, Benjamin
• Lucas, Mary
• Malinauskas, Tomas
• Martin, Hilary C
• Lockstone, Helen E
• Cazier, Jean-Baptiste
• Chapel, Helen M
• Knight, Julian C
• Patel, Smita Y

Titel

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders

Ist Teil von

• Clinical immunology (Orlando, Fla.), 2015-10, Vol.160 (2), p.301-314

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in < 5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B , TNFRSF13C , LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways.