Three faces of recombination activating gene 1 (RAG1) mutations

Severe combined immune deficiency (SCID) is a group of genetic disorder associated with development of T- and/or B-lymphocytes. Recombination-activating genes (RAG1/2) play a critical role on VDJ recombination process that leads to the production of a broad T-cell receptor (TCR) and B-cell receptor (BCR) repertoire in the development of T and B cells. RAG1/2 genes mutations result in various forms of primary immunodeficiency, ranging from classic SCID to Omenn syndrome (OS) to atypical SCID with such as granuloma formation and autoimmunity. Herein, we reported 4 patients with RAG1 deficiency: classic SCID was seen in two patients who presented with recurrent pneumonia and chronic diarrhoea, and failure to thrive. OS was observed in one patient who presented with chronic diarrhoea, skin rash, recurrent lower respiratory infections, and atypical SCID was seen in one patient who presented with Pyoderma gangrenosum (PG) and had novel RAG1 mutation

Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. Methods: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. Results: Analyses revealed a mutation detection sensitivity of 97.3 %, an average coverage per gene of 98.0 %, and adequate coverage over 98.6 % of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38 %). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. Conclusions: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.Peer reviewe

İnek sütü proteini allerjisinden kaynaklanan hemorajik gastrit

İnek s&uuml;t&uuml; proteini allerjisi bebeklik d&ouml;neminde sıklıkla g&ouml;r&uuml;l&uuml;r. İnek s&uuml;t&uuml; proteini allerjisinde y&uuml;zeysel gastritten hemorajik gastrite kadar &ccedil;ok farklı histopatolojik tutulum olabilir. İnek s&uuml;t&uuml; allerjili &ccedil;ocuklarda, inat&ccedil;ı kusma ve hematemez durumunda hemorajik gastritten ş&uuml;phelenilmelidir. Endoskopi ve biyopsi tanıda &ouml;nemlidir. Anahtar Kelimeler: &nbsp; &nbsp; Allerji, hemoraji, gastrit Cow&rsquo;s milk protein allergy is frequently seen in infancy. Its findings can be diverse, including different histopathological involvement ranging from a superficial to hemorrhagic gastritis. Children presenting with resistant emesis, hematemesis and hemorrhagic gastritis should be investigated for cow&rsquo;s milk allergy. Endoscopy and biopsy are important in the diagnosis. Key words &nbsp; &nbsp; : Allergy, hemorrhagic, gastritis</p

Exhaled breath condensate Annexin A5 levels in exercise-induced bronchoconstriction in asthma: a preliminary study

Background and objective: The pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma is incompletely understood. The role of exhaled breath condensate (EBC) annexin A5, which is an anti-inflammatory mediator, has not been investigated. The purpose of this study is to evaluate EBC annexin A5 levels in EIB in asthmatic children