Publications by authors named "Matthieu Bouaziz"

Population stratification is a confounder of genetic association studies. In analyses of rare variants, corrections based on principal components (PCs) and linear mixed models (LMMs) yield conflicting conclusions. Studies evaluating these approaches generally focused on limited types of structure and large sample sizes.

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Many methods for rare variant association studies require permutations to assess the significance of tests. Standard permutations assume that all individuals are exchangeable and do not take population stratification (PS), a known confounding factor in genetic studies, into account. We propose a novel strategy, LocPerm, in which individual phenotypes are permuted only with their closest ancestry-based neighbors.

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Article Synopsis
  • Autosomal recessive (AR) STAT1 deficiency significantly impairs the immune response to various infections, making patients highly susceptible to viral and mycobacterial diseases.
  • An international study of 32 patients revealed that complete deficiency leads to more severe outcomes, including a higher mortality rate and serious reactions to vaccines.
  • Hematopoietic stem cell transplantation shows promise as a treatment, with a 64% survival rate for those who undergo the procedure, underscoring the importance of early diagnosis and differentiation between complete and partial deficiency forms.
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Whole-exome sequencing (WES) has facilitated the discovery of genetic lesions underlying monogenic disorders. Incomplete penetrance and variable expressivity suggest a contribution of additional genetic lesions to clinical manifestations and outcome. Some monogenic disorders may therefore actually be digenic.

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Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls ( = 8.37 × 10; odds ratio, 89.

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Article Synopsis
  • - The study investigates isolated congenital asplenia (ICA), a rare condition affecting the lymphoid organ, linked to mutations in the ribosomal protein SA gene, with a significant number of cases showing a connection to protein-coding mutations and some affecting mRNA splicing.
  • - New research identified 11 additional mutations in the ribosomal protein SA gene and revealed that a majority of the studied kindreds (41%) and over half of patients (55%) have mutations that can lead to ICA.
  • - Notably, the study highlights the variable expressiveness of these mutations, with some demonstrating incomplete penetrance, suggesting that not all individuals with mutations will develop symptoms of ICA.
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Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of (encoding EVER1) or (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients.

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Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another.

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Article Synopsis
  • Heterozygous dominant-negative mutations are linked to a common form of hyper-immunoglobulin E syndrome (HIES), while a newly identified autosomal recessive form is caused by loss-of-function mutations in the ZNF341 gene.
  • ZNF341 is crucial as a transcription factor in the nucleus, where it binds to DNA to regulate various genes, including those involved in immune response.
  • Patients lacking ZNF341 show impaired production and function of STAT3, leading to deficiencies in specific immune cells and altered inflammatory responses.
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Purpose: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency predisposing congenitally affected individuals to diseases caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccine strains and environmental mycobacteria. IL-12p40 deficiency is a genetic etiology of MSMD resulting in impaired IL-12- and IL-23-dependent IFN-γ immunity. Most of the reported patients with IL-12p40 deficiency originate from Saudi Arabia (30 of 52) and carry the recurrent IL12B mutation c.

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Most humans are exposed to (Tw). Whipple's disease (WD) strikes only a small minority of individuals infected with Tw (<0.01%), whereas asymptomatic chronic carriage is more common (<25%).

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Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility.

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Objective: Recognition of the well-known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc.

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Inferring the structure of populations has many applications for genetic research. In addition to providing information for evolutionary studies, it can be used to account for the bias induced by population stratification in association studies. To this end, many algorithms have been proposed to cluster individuals into genetically homogeneous sub-populations.

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Introduction: Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH.

Objective: To explore the genetic bases of SSc-PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members.

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Recent advances in Molecular Biology and improvements in microarray and sequencing technologies have led biologists toward high-throughput genomic studies. These studies aim at finding associations between genetic markers and a phenotype and involve conducting many statistical tests on these markers. Such Please confirm the changes in the sentence "Such a wide.

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Objective: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk.

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Genome-Wide Association Studies are powerful tools to detect genetic variants associated with diseases. Their results have, however, been questioned, in part because of the bias induced by population stratification. This is a consequence of systematic differences in allele frequencies due to the difference in sample ancestries that can lead to both false positive or false negative findings.

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