Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system

The Effect of Food Allergen Exclusion on the Growth of Saudi Children

With a variety of symptoms that can impede children’s development, food allergies are an important public health concern. With the help of information from the King Fahad Medical City Hospital in Riyadh, we looked at how restricting certain foods affected the growth of Saudi children who had food allergies. An anonymous self-administered questionnaire asking about the individuals’ demographics and their restricted eating habits was completed by 72 children (48 boys and 24 girls) between the ages of 2 and 14. The sensitivity of six allergens (hen eggs, cow milk, fish, wheat, peanuts, and soybeans), anthropometric indices, specific Immunoglobulin E (IgE) levels, and sensitivity were examined. The Statistical Package for Social Science (SPSS), version 26, was used to analyze the data. Chi-square and t-tests were used to examine the relationships between various category variables. According to the findings, most of the mothers of the children were between the ages of 30 and 40 (80.6%), had a college degree (72.3%), were unemployed (59.7%), and had a monthly family income between 5000 and 15,000 SAR (69.4%). Both sexes had specific IgE antibodies for allergens in classes 2 and 3, with boys having noticeably (p ≤ 0.05) higher quantities than girls. While females were more sensitive to fish and peanuts, boys were more likely than girls to show specific IgE sensitivity to egg white, cow milk, wheat, and soybeans. Both sexes’ allergy levels were considerably (p ≤ 0.01) higher in children aged 5.01 to 10 than in other age groups. In terms of classifications of thinness, overweightness, and obesity, boys were slenderer than girls, and a greater percentage of boys than girls were overweight or obese. The exclusion of hen eggs, cow milk, wheat, and peanuts from the diet had a significant and detrimental effect on body mass index (BMI) and height-for-age ratio among children with impaired growth, in contrast to the demographic factors, which had a significant and favorable effect on the growth of other children. In conclusion, restrictions on food allergens impairs growth in Saudi children, particularly boys’ growth

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Contains fulltext : 204759.pdf (publisher's version ) (Open Access

Testutrustning för böjning av massiva ämnen av bok och björk

Upprättat; 2007; 20141022 (dicsan

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Background: Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test. Methods: In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors. Results: For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%). Conclusion: Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data

Additional file 2: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S2. Shows all causative mutations identified in 72 patients from 68 families suffering from primary immunodeficiencies. (XLSX 17 kb

Additional file 3: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S3. Variants of unknown significance (class 3) and variants in TRAF3 identified in 17 patients suffering from primary immunodeficiencies. (XLSX 11 kb

Additional file 4: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S4. (A) The number of patients with isolated or combined infections, and (B) the number of patients with isolated or combined immunophenotypes, and the percentage for which we have reported a genetic diagnosis. (XLSX 11 kb

Additional file 5: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S5. Quality information of the WES technology, with the mean target coverage, and the % of bases with >â 20Ă coverage. (XLSX 22 kb