Yuval Itan
A5021904235- Immunodeficiency and Autoimmune Disorders
- Genomics and Rare Diseases
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- Blood disorders and treatments
- Genetic Associations and Epidemiology
- Digestive system and related health
- Genomics and Phylogenetic Studies
- Inflammatory Bowel Disease
- interferon and immune responses
- Congenital Heart Disease Studies
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- Genomic variations and chromosomal abnormalities
- Immune Response and Inflammation
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Machine Learning in Bioinformatics
- Immune responses and vaccinations
- Congenital heart defects research
- SARS-CoV-2 and COVID-19 Research
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Fungal Infections and Studies
Child Health and Development Institute
2021-2025
Icahn School of Medicine at Mount Sinai
2017-2025
KU Leuven
2024
Rockefeller University
2011-2024
Sichuan University
2022
West China Hospital of Sichuan University
2022
Cardiff University
2022
New York Proton Center
2017
University College London
2008-2016
University of Tehran
2016
Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 47 patients from 20 kindreds with AD CMCD. Previously described mutant alleles are loss-of-function and cause predisposition to mycobacterial impaired STAT1-dependent cellular responses IFN-γ. Other AR intracellular bacterial viral diseases, IFN-α/β, IFN-γ,...
We compared whole-exome sequencing (WES) and whole-genome (WGS) in six unrelated individuals. In the regions targeted by WES capture (81.5% of consensus coding genome), mean numbers single-nucleotide variants (SNVs) small insertions/deletions (indels) detected per sample were 84,192 13,325, respectively, for WES, 84,968 12,702, WGS. For both SNVs indels, distributions coverage depth, genotype quality, minor read ratio more uniform WGS than WES. After filtering, a 74,398 (95.3%) high-quality...
Lactase persistence (LP) is common among people of European ancestry, but with the exception some African, Middle Eastern and southern Asian groups, rare or absent elsewhere in world. gene haplotype conservation around a polymorphism strongly associated LP Europeans (−13,910 C/T) indicates that derived allele recent origin has been subject to strong positive selection. Furthermore, ancient DNA work shown −13,910*T (derived) was very early Neolithic central Europeans. It unlikely would...
Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence one clearest examples niche humans. enzyme responsible for digestion milk sugar lactose and its production decreases after weaning phase most mammals, including Some humans, however, continue to produce lactase throughout adulthood, a trait known as persistence. In European populations, single mutation (-13910*T)...
A surprising immune twist for RORC The system needs its full array of soldiers—including cells and the molecules they secrete—to optimally protect host. When this isn't case, minor infections can become chronic or even deadly. Markle et al. report discovery seven individuals carrying loss-of-function mutations in RORC, which encodes transcription factors RORγ RORγT. These lacked that produce cytokine interleukin-17, causing them to suffer from candidiasis. RORC-deficient also exhibited...
Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families four different ethnic groups. These were homozygous for one null mutations, that seen P1. They displayed mycobacterial and/or infections, but no HIES. All eight impaired...
The ability of adult humans to digest the milk sugar lactose - lactase persistence is a dominant Mendelian trait that has been subject extensive genetic, medical and evolutionary research. Lactase common in people European ancestry as well some African, Middle Eastern Southern Asian groups, but rare or absent elsewhere world. recent identification independent nucleotide changes are strongly associated with different populations worldwide led possibility genetic tests for trait. However, it...
Inherited, complete deficiency of human HOIL-1, a component the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report clinical description molecular analysis novel inherited disorder LUBAC complex. A patient with multiorgan combined immunodeficiency, subclinical amylopectinosis, systemic lymphangiectasia, is homozygous for mutation in HOIP, gene encoding catalytic LUBAC. The missense allele (L72P, PUB domain) at least...
Significance The protein-coding exome of a patient with monogenic disease contains about 20,000 variations, which only one or two are causing. When attempting to select disease-causing candidate mutation(s), challenge is filter out as many false-positive (FP) variants possible. In this study, we describe the gene damage index (GDI), metric for nonsynonymous mutational load in each general population. We show that GDI an efficient gene-level method filtering FP genes highly damaged
Whole exome sequencing (WES) has proven an effective tool for the discovery of genetic defects in patients with primary immunodeficiencies (PIDs). However, success dissecting etiology common variable immunodeficiency (CVID) been limited. We outline a practical framework using WES to identify causative these subjects. Exome Sequencing was performed on 50 subjects diagnosed CVID who had at least one following criteria: early onset, autoimmune/inflammatory manifestations, low B lymphocytes,...
Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause unknown majority cases, and less than 10% patients have a family history disease. Most normal numbers B cells but lack plasma cells.
Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that present quantitatively or functionally deficient. Impaired humoral is also common. Patients have severe infections, autoimmunity, both. The specific molecular, cellular, and clinical features many types combined remain unknown. Methods We performed genetic cellular immunologic studies involving five unrelated children with early-onset invasive bacterial viral lymphopenia, defective...
Homozygosity for the P1104A missense variant of TYK2 Janus kinase is common monogenic etiology primary tuberculosis.
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA ACT1 deficiencies autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, 37 yr isolated CMC, who display AR IL-17RC deficiency. The are homozygous for different...
Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rβ1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, mucocutaneous candidiasis. Susceptibility to these infections is thought be due impairments IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here IL-12Rβ2 IL-23R deficiency, lacking responses IL-12 IL-23 only, all whom, unexpectedly, display...
Spleen Knockout Explained Isolated congenital asplenia (ICA) is a rare disorder where patients are born without spleen and at increased risk of bacterial infection but have no other developmental abnormalities. Through sequence analysis familial sporadic cases, Bolze et al. (p. 976 , published online 11 April) found that ICA carry mutations in the gene encoding ribosomal protein SA as result express about half normal amount this protein. The mechanism by which reduced expression housekeeping...
Significance Chronic mucocutaneous candidiasis (CMC) is defined as persistent or recurrent infections of the skin and/or mucosae by commensal fungi Candida genus. It often seen in patients with T-cell deficiencies, whether inherited acquired, who typically suffer from multiple infectious diseases. Rare are otherwise healthy and display isolated CMC, which segregates a Mendelian trait. In 2011, we described first genetic cause autosomal recessive (AR), complete IL-17 receptor A (IL-17RA)...