Hofer M.,University of Lausanne |
Pillet P.,Paediatric Rheumatology |
Cochard M.,University of Lausanne |
Berg S.,Gothenburg University |
And 12 more authors.
Rheumatology (United Kingdom) | Year: 2014
Objectives: The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. Methods: We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Results: Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. Conclusion: We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Messaed C.,McGill University |
Chebaro W.,McGill University |
Di Roberto R.B.,McGill University |
Rittore C.,Unite Medicale des Maladies Auto Inflammatoires |
And 16 more authors.
Journal of Medical Genetics | Year: 2011
Background: NLRP7 mutations are responsible for recurrent molar pregnancies and associated reproductive wastage. To investigate the role of NLRP7 in sporadic moles and other forms of reproductive wastage, the authors sequenced this gene in a cohort of 135 patients with at least one hydatidiform mole or three spontaneous abortions; 115 of these were new patients. Methods/Results: All mutations were reviewed and their number, nature and locations correlated with the reproductive outcomes of the patients and histopathology of their products of conception. The presence of NLRP7 mutations was demonstrated in two patients with recurrent spontaneous abortions, and some rare non-synonymous variants (NSVs), present in the general population, were found to be associated with recurrent reproductive wastage. These rare NSVs were shown to be associated with lower secretion of interleukin 1β and tumour necrosis factor and therefore to have functional consequences similar to those seen in cells from patients with NLRP7 mutations. The authors also attempted to elucidate the cause of stillbirths observed in 13% of the patients with NLRP7 mutations by examining available placentas of the stillborn babies and live births from patients with mutations or rare NSVs. A number of severe to mild placental abnormalities were found, all of which are known risk factors for perinatal morbidity. Conclusions: The authors recommend close follow-up of patients with NLRP7 mutations and rare NSVs to prevent the death of the rare or reduced number of babies that reach term.
Muhlstein J.,Pole de Gynecologie obstetrique et Reproduction |
Golfier F.,University of Lyon |
Frappart L.,Service dAnatomie Pathologique |
Poulizac G.,Cabinet de Gynecologie |
And 4 more authors.
Gynecologie Obstetrique Fertilite | Year: 2010
Repetitive moles are rare. They are either sporadic or familial, with or without consanguinity. Some of them can be explained by a NLRP7 mutation, which causes genomic parental imprinting alteration, with a preferential paternal phenotypic expression. Currently, no effective therapeutic solution has been developed. Among the 1687 patients declared to the French Trophoblastic Disease Reference Center, 13 presented at least two hydatidiform moles, thus less than 1% of the patients. A mutation of the NLRP7 gene was shown in six of 12 tested patients (50%) among whom three presented a homozygous mutation and three a heterozygous mutation. For an affected patient, type of mole can indifferently be a complete hydatidiform mole or a partial hydatidiform mole. We describe these cases and compare them to those already published. © 2010 Elsevier Masson SAS. All rights reserved.
Muhlstein J.,University of Lyon |
Golfier F.,University of Lyon |
Rittore C.,Unite Medicale des Maladies Auto inflammatoires |
Hajri T.,University of Lyon |
And 5 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2011
Objectives: The NLRP7 gene (19q13.42) is associated with recurrent and/or familial hydatidiform moles. Several mutations, histopathological types and reproductive outcomes have been described. We studied our recurrent hydatidiform mole cases recorded since 1999 in order to identify links between clinic, histology and genetics. Study: We present here the gestational history and the spectrum of NLRP7 mutations in our French series. Design: We performed a retrospective study from clinical forms received for genetic diagnosis. Cases declaration was based on a voluntary initiative coming from French practitioners, subjected to patients' agreement. Results: Among 12 recurrent hydatidiform moles investigated, we identified 3 cases of confirmed homozygous NLRP7 mutation and 3 cases of heterozygous NLRP7 mutation. One patient bore a novel mutation p.Leu880Ser in a homozygous state. Conclusions: We here identified a new homozygous NLRP7 mutation. Unfortunately, no modern therapeutic option has proven effective to obtain evolutive pregnancies. Then, fundamental and clinical researches seem to be necessary. Moreover, collecting RHM cases is essential. © 2011 Elsevier Ireland Ltd.
Grandemange S.,Unite Medicale des Maladies Auto inflammatoires |
Aksentijevich I.,National Human Genome Research Institute |
Jeru I.,University Pierre and Marie Curie |
Gul A.,Istanbul University |
Touitou I.,Unite Medicale des Maladies Auto inflammatoires
Genes and Immunity | Year: 2011
Familial Mediterranean fever (FMF) is a hereditary recurrent fever associated with mutations in the gene MEFV encoding pyrin. It is expressed mainly in neutrophils and macrophages, and modulates the production of the potent pro-inflammatory cytokine interleukin-1κΒ through regulation of nuclear factor-B and caspase-1β. The MEFV gene expression depends on multiple levels of regulation. Sequence variants located in the promoter and at the 3′-untranslated region of the gene modulate this expression. Two studies demonstrated decreased mRNA levels in FMF patients compared with healthy subjects, whereas two others found no significant differences. The diverse experimental settings may have resulted in variable quantification of the 15 splice variants that have been identified recently. Some of these isoforms are regulated by nonsense-mediated decay in both cell- and transcript-specific manner, and may be differentially translated in THP1 cells. In addition, pyrin may be cleaved by caspase 1. The full-length pyrin was less abundant than the cleaved fragment in mononuclear cells from FMF patients than in controls, whereas the opposite was observed in granulocytes. Altogether, the regulation of MEFV expression is more complex than anticipated in both physiological and pathological conditions. Its deregulation is likely to alter the inflammasome function and subsequently result in uncontrolled inflammation as seen in FMF. © 2011 Macmillan Publishers Limited All rights reserved.
Khaib Dit Naib O.,Abou Bekr Belkaid University Tlemcen |
Aribi M.,Abou Bekr Belkaid University Tlemcen |
Idder A.,Etablissement Hospitalier Specialise en Ophtalmologie |
Chiali A.,Oran University of Science and Technology - Mohamed Boudiaf |
And 6 more authors.
Frontiers in Immunology | Year: 2013
Objective: We have conducted the first study of the association of interleukin (IL)-10, tumor necrosis factor alpha (TNF-α), and IL23R-IL12RB2 region single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) in Western Algeria. Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPs from the IL10 promoter [c.-819T > C (rs1800871), c.-592A > C (rs1800872)], 6 SNPs from the TNF-α promoter [c.-1211T > C (rs1799964), c.-1043C > A (rs1800630), c.-1037C > T (rs1799724), c.-556G > A (rs1800750), c.-488G > A (rs1800629), and c.-418G > A (rs361525)], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A > C (rs12119179), g.67740092G > A (rs11209032), and g.67760140T > C (rs924080)]. Results: The minor alleles c.-819T and c.-592A were significantly associated with BD [odds ratio (OR) = 2.18; 95% confidence interval (CI) 1.28-3.73, p = 0.003]; whereas, there was weaker association between TNF-α promoter SNPs or IL23R-IL12RB2 region and disease risk. Conclusion: Unlike the TNF-α and the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria. © 2013 Khaib Dit Naib, Aribi, Idder, Chiali, Sairi, Touitou, Lefranc and Barat-Houari.
PubMed | Montpellier University, Nimes University Hospital Center, Unite Medicale des Maladies Auto Inflammatoires and Abou Bekr Belkaid University Tlemcen
Type: | Journal: Genetics research international | Year: 2014
Background. Venous malformations (VM) result from an error in vascular morphogenesis. The first gene suspected in their development is the TEK gene (tyrosine kinase, endothelial). Mutations of this gene have been identified in several Belgian families with a dominant form of the disease. Therefore, we investigated whether mutations in this TEK gene could explain the MV development in patients of families from Tlemcen region (north-western Algeria). Methods. Genomic DNA was extracted from leucocytes of ten patients. The search for mutations in all the 23 exons and in the 5 and 3 intronic sequences flanking the TEK gene was performed using PCR amplification and direct sequencing of amplified genomic DNA. Additionally, a search for somatic mutations of the gene TEK was performed on a biopsy of the venous malformation from one of the ten eligible patients. Results. The sequencing of the 23 exons of the TEK gene revealed neither germinal mutation in our ten patients nor somatic mutation in the tissue of the biopsy. Conclusion. The absence of mutation in the TEK gene in the population studied suggests that the TEK gene is not necessarily involved in the onset of VM; its association with these malformations may differ from one population to another.
PubMed | Unite medicale des maladies Auto inflammatoires
Type: Journal Article | Journal: Rheumatology (Oxford, England) | Year: 2012
Behets disease (BD) is a multisystemic inflammatory disease, mainly characterized by recurrent oral and genital ulcers (GUs), skin lesions and uveitis. Several genetic factors such as the TNF- gene have been evaluated as contributors to the pathogenesis of BD. We aimed to evaluate the association between six TNF- SNPs and susceptibility to BD, or the major clinical manifestations, in Moroccan patients. The six SNPs studied were: c.-1211C>T (rs1799964), c.-1043C>A (rs1800630), c.-1037C>T (rs1799724), c.-556G>A (rs1800750), c.-488G>A (rs1800629) and c.-418G>A (rs361525), known as -1031T>C, -863C>A, -857C>T, -376G>A, 308G>A and -238G>A, respectively.SNPs were genotyped by direct sequencing in 120 unrelated Moroccan BD and 112 ethnically matched healthy controls. Allele and genotype distributions were compared between groups using chi-square or Fishers exact tests.The frequency of the -1211C allele was higher in (i) BD patients than in controls [P=0.02, odds ratio (OR)=1.68, 95% CI 1.10, 2.56] and in (ii) patients with GUs than in those without (P=0.002, OR=3.84, 95% CI 1.55, 9.49). The -418A frequency was lower in patients with uveitis (P=0.0003, OR=0.19, 95% CI 0.07, 0.5).We report the first association between BD and TNF- SNPs in Moroccan patients. We mainly observed that -1211C constitutes a susceptibility allele for both BD and GU, as previously reported for other populations. The -418A allele could be considered as a good prognostic factor for anterior uveitis, in Moroccan BD patients.