Identification of an autosomal recessive mode of inheritance in paediatric Behçet's families by segregation analysis

Molinari, Noelle-Angelique; Paut, Isabelle Koné; Manna, R.; Demaille, Jacques; Daurès, Jean Pierre; Touitou, Isabelle

doi:10.1002/ajmg.a.20136

Cited by 33 publications

(11 citation statements)

References 14 publications

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“…Accordingly, most patients with vasculitis acknowledged autoimmune factors as causal in the disease process. Of all types of vasculitis under study, the strongest scientific evidence for a hereditary component of disease has been reported in Behçet’s disease 25–27 , and hereditary factors among patients with Behçet’s disease were indeed more commonly attributed as causal than in other forms of vasculitis. Few environmental exposures have been associated with vasculitis.…”

Section: Discussionmentioning

confidence: 99%

Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis

et al. 2014

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Objectives Patients vary in their beliefs related to the cause of serious illness. The impact of these beliefs among patients with systemic vasculitis is not known. This study aimed to describe causal attributions about disease-onset and relapse in systemic vasculitis and to examine whether causal beliefs a) differ by type of vasculitis; and b) are associated with negative health outcomes. Methods Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease-onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. Results 692 patients representing 9 forms of vasculitis completed the questionnaire. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with few notable exceptions primarily in Behçet’s disease. Beliefs differed about causes of disease-onset versus relapse. Specific beliefs about disease-onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Conclusion Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients’ causal beliefs.

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Section: Discussionmentioning

confidence: 99%

Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis

et al. 2014

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“…Stronger familial aggregation was observed among early onset BD patients [12] compared with individuals with disease onset in adulthood. Analysis of BD pediatric patient families suggested an autosomal recessive mode of inheritance by segregation analysis [17]. However, no particular Mendelian inheritance patterns were shown from analysis of BD including all ages of onset [17, 18].…”

Section: Genetic Factorsmentioning

confidence: 99%

“…Analysis of BD pediatric patient families suggested an autosomal recessive mode of inheritance by segregation analysis [17]. However, no particular Mendelian inheritance patterns were shown from analysis of BD including all ages of onset [17, 18]. A study in the Turkish population reported a high sibling recurrence (4.2%), and estimated a high sibling recurrence risk ratio (λs) (11.4 – 52.5), which is the ratio between the risk of being affected among siblings of patients to the disease risk in the general population, a widely used indicator for familial aggregation [19, 20].…”

Section: Genetic Factorsmentioning

confidence: 99%

The immunogenetics of Behçet's disease: A comprehensive review

Takeuchi

Kastner

Remmers

2015

Journal of Autoimmunity

178

127

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Behçet’s disease is a chronic multisystem inflammatory disorder characterized mainly by recurrent oral ulcers, ocular involvement, genital ulcers, and skin lesions, presenting with remissions and exacerbations. It is thought that both environmental and genetic factors contribute to its onset and development. Although the etiology of Behçet’s disease remains unclear, recent immunogenetic findings are providing clues to its pathogenesis. In addition to the positive association of HLA-B*51, which was identified more than four decades ago, and which has since been confirmed in multiple populations, recent studies report additional independent associations in the major histocompatibility complex class I region. HLA-B*15, -B*27, -B*57, and -A*26 are independent risk factors for Behçet’s disease, while HLA-B*49 and – A*03 are independent class I alleles that are protective for Behçet’s disease. Genome-wide association studies have identified associations with genome-wide significance (P < 5 × 10−8) in the IL23R–IL12RB2, IL10, STAT4, CCR1-CCR3, KLRC4, ERAP1, TNFAIP3, and FUT2 loci. In addition, targeted next-generation sequencing has revealed the involvement of rare nonsynonymous variants of IL23R, TLR4, NOD2, and MEFV in Behçet’s disease pathogenesis. Significant differences in gene function or mRNA expression associated with the risk alleles of the disease susceptibility loci suggest which genes in a disease-associated locus influence disease pathogenesis. These genes encompass both innate and adaptive immunity and confirm the importance of the predominant polarization towards helper T cell (Th) 1 versus Th2 cells, and the involvement of Th17 cells. In addition, epistasis observed between HLA-B*51 and the risk coding haplotype of the endoplasmic reticulum-associated protease, ERAP1, provides a clue that an HLA class I-peptide presentation-based mechanism contributes to this complex disease.

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“…This evidence was further supported by a segregation analysis after stratification of BD families into paediatric and non-paediatric groups, which detected a Mendelian autosomal recessive transmission only in paediatric families. In contrast, no evidence for Mendelian inheritance was observed in patients with BD and more typical age of onset criteria [75]. Three-fourths of subjects complained of headache, often associated with other alarming neurological findings such as nausea, vomiting, or papilledema (11 of 16 detailed cases).…”

Section: Discussionmentioning

confidence: 99%

Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

Mora

Menozzi

Orsoni

et al. 2013

Orphanet Journal of Rare Diseases

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Neuro-Behçet’s disease (NBD) involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension); thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD); the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1). We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases). In 19/53 patients (36%), neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine). Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our review and personal experience, a delayed diagnosis, and the consequently delayed immunosuppressive treatment, may favour permanent sequelae, in particular, optic atrophy.

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Identification of an autosomal recessive mode of inheritance in paediatric Behçet's families by segregation analysis

Cited by 33 publications

References 14 publications

Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis

Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis

The immunogenetics of Behçet's disease: A comprehensive review

Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

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