Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency.

Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency. Cell Mol Immunol. 2020 Aug 17;: Authors: Edwards ESJ, Bosco JJ, Ojaimi S, O'Hehir RE, van Zelm MC Abstract Predominantly antibody deficiency (PAD) is the most prevalent form of primary immunodeficiency, and is characterized by broad clinical, immunological and genetic heterogeneity. Utilizing the current gold standard of whole exome sequencing for diagnosis, pathogenic gene variants are only identified in less than 20% of patients. While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis, many other genes may remain as yet undefined to enable definitive diagnosis, prognostic monitoring and targeted therapy of patients. Considering that many patients display a relatively late onset of disease presentation in their 2nd or 3rd decade of life, it is questionable whether a single genetic lesion underlies disease in all patients. Potentially, combined effects of other gene variants and/or non-genetic factors, including specific infections can drive disease presentation. In this review, we define (1) the clinical and immunological variability of PAD, (2) consider how genetic defects identified in PAD have given insight into B-cell immunobiology, (3) address recent technological advances in genomics and the challenges associated ...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research