A novel single variant in the MEFV gene causing Mediterranean fever and Behçet's disease: a case report.

BACKGROUND: Familial Mediterranean fever is an autoinflammatory disease of unknown etiology, characterized clinically by recurrent attacks of sudden-onset fever with arthralgia and/or thoracoabdominal pain and pathogenetically by autosomal recessive inheritance due to a mutation in the MEFV gene. Behçet's disease is an inflammatory disease characterized by recurrent oral and genital aphthous ulcerations, uveitis, and skin lesions. Preliminarily, our literature review suggested that patients with familial Mediterranean fever who also have Behçet's disease have only a single mutated familial Mediterranean fever gene. The MEFV gene mutation responsible for familial Mediterranean fever is probably a susceptibility factor for Behçet's disease, particularly for patients with vascular involvement, and both disorders can occur concurrently in a patient, as in the present case. CASE PRESENTATION: A 10-year-old girl of Moroccan origin presented to our institution for genetic consultation for genetic testing of the MEFV gene. She had fever associated with abdominal and diffuse joint pain in addition to headache. These symptoms have oriented pediatricians to familial Mediterranean fever. The evolution was marked by Behçet's syndrome symptoms. Sanger sequencing followed by complete exome sequencing analysis of the MEFV gene for the proband mutation revealed a novel variant. We conclude that the novel single variant c.2078 T > A (p.Met693Lys) could be responsible for the association of familial Mediterranean fever and Behçet's disease. CONCLUSION: To the best of our knowledge, this is the first report of a new variant in exon 10 of the MEFV gene in a Moroccan family. This novel variant should be listed in the MEFV sequence variant databases.

Next Generation Sequencing identifies mutations in GNPTG gene as a cause of familial form of scleroderma-like disease.

BACKGROUND: Scleroderma is a multisystem disease, characterized by fibrosis of skin and internal organs, immune dysregulation, and vasculopathy. The etiology of the disease remains unknown, but it is likely multifactorial. However, the genetic basis for this condition is defined by multiple genes that have only modest effect on disease susceptibility. METHODS: Three Moroccan siblings, born from non-consanguineous Moroccan healthy parents were referred for genetic evaluation of familial scleroderma. Whole Exome Sequencing was performed in the proband and his parents, in addition to Sanger sequencing that was carried out to confirm the results obtained. RESULTS: Mutation analysis showed two compound heterozygous mutations c.196C>T in exon 4 and c.635_636delTT in exon 9 of GNPTG gene. Sanger sequencing confirmed these mutations in the affected patient and demonstrated that their parents are heterozygous carriers. CONCLUSION: Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype-genotype correlation of Mucolipidosis Type III gamma. This report also highlights the diagnostic utility of Next Generation Sequencing particularly when the clinical presentation did not point to specific genes.

Consensus classification criteria for paediatric Behçet's disease from a prospective observational cohort: PEDBD.

BACKGROUND: We aimed to describe the main features of Behçet's disease (BD) in children in the largest prospective cohort to date and to propose a classification. METHODS: An international expert consensus group was formed to define a data set of minimal symptoms for the inclusion of patients. Patients were entered prospectively during 66 months. Experts classified patients on a consensus basis. The concordance of two international classifications was analysed in confirmed patients with BD. Comparisons of subgroups of patients helped define consensus criteria. BD-associated clinical manifestations were also investigated in three control diseases extracted from an independent data set (Eurofever). FINDINGS: In total, 42 centres from 12 countries included 230 patients; data for 219 (M/F ratio=1) could be analysed. The experts classified 156 patients (71.2%) as having confirmed BD. Males more often than females showed cutaneous, ocular and vascular symptoms and females more often genital aphthosis. Age at disease onset and skin and vascular involvement were lower for European than non-European children. Oral aphthosis was the presenting sign for 81% (179/219) of patients. The mean delay to the second symptom was 2.9±2.2 years. International classifications were not concordant with the expert classification. Our paediatric classification contains six categories, a minimum of three signs (each in a distinct category) defining paediatric BD. Three clinical signs discriminated our cohort from the Eurofever cohorts. INTERPRETATION: We present a comprehensive description of a large cohort of patients from both European and non-European countries and propose the first classification of paediatric BD for future therapeutic trials.

Effect of body composition on bone mineral density in Moroccan patients with juvenile idiopathic arthritis.

INTRODUCTION: The link between bone mass and body composition is widely recognized, but only few works were selectively performed on subjects with juvenile idiopathic arthritis. The aim of our study was to investigate the effect of body composition on bone mineral density (BMD) in Moroccan patients with juvenile idiopathic arthritis. METHODS: Thirty three children with juvenile idiopathic arthritis (JIA) were included in a cross-sectional study. The diagnosis of JIA was made according to the criteria of the International League of Association of Rheumatology (ILAR). Body mass index (BMI) was calculated from the ratio of weight/height(2)(kg/m(2)). Pubertal status was determined according to the Tanner criteria. Bone status, body composition and bone mineral content (BMC) were analyzed by using dual-energy X-ray absorptiometry (DXA). BMD was assessed at the lumbar spine (L1-L4) and at total body in (g/cm(2)). Total body fat tissue mass (FTM) and lean tissue mass (LTM) were also analyzed by DXA and expressed in kilograms. In children, low BMD was defined as a Z-score less than -2 and osteoporosis was defined as a Z-score less than -2 with a fracture history. RESULTS: A cross-sectional study was conducted in 33 Moroccan patients with JIA aged between 4 and 16 years, Fat mass was not related to bone density; in contrast, BMD was positively associated to LTM in total body(r = =0.41, p= 0.04) but not in lumbar spine (r = 0.29, p= 0.17). There exist significant correlation between BMC and BMD in total body (r = 0.51, p = 0.01). CONCLUSION: This study suggests that the LTM is a determining factor of the BMD during adolescence. Other studies with a broader sample would be useful to confirm this relation.

Vitamin D concentrations and disease activity in Moroccan children with juvenile idiopathic arthritis.

BACKGROUND: In addition to its important metabolic activities, vitamin D also contributes to the regulation of the immune system. The aim of this study was to assess the relationship between hypovitaminosis D and disease activity in Moroccan children with juvenile idiopathic arthritis (JIA). METHODS: In this cross-sectional study, forty children with JIA were included, all having been diagnosed according to the classification criteria of International League of Associations for Rheumatology (ILAR). The children underwent anthropometric assessment and clinical evaluation. Disease activity was measured using the Disease Activity Score in 28 joints (DAS28) for polyarticular and oligoarticular JIA and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for enthesitis-related arthritis. Serum 25-hydroxyvitamin [25(OH)D] D2 and D3 were measured using radioimmunoassay (RIA). Hypovitaminosis D was defined as serum 25(OH)D <30 ng/ml. RESULTS: The average age of participants was 11 years ± 4.23. Hypovitaminosis D was observed in 75% of patients. In univariate analyses, 25(OH)D levels were negatively associated with DAS28 for polyarticular and oligoarticular JIA. No significant relationship was found between 25(OH)D levels and BASDAI for juvenile spondylarthropathy. In multivariate linear regression analysis, no association persisted between 25(OH)D levels and DAS28. CONCLUSIONS: Our study suggested that serum levels of vitamin D were low in Moroccan children with JIA disease. Future studies with a larger population are needed to confirm our results.

Impact of juvenile idiopathic arthritis on schooling.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common arthropathy of childhood. Different diseases affect school attendance to varying degrees. The aim of this study was to assess the impact of juvenile idiopathic arthritis (JIA) on Moroccan children's schooling. METHODS: Thirty-three children with JIA were included in this study, having been previously diagnosed according to the classification criteria of the International League of Associations for Rheumatology (ILAR). Seventy-four healthy children were recruited to serve as controls. Data was obtained for all children on their school level, educational performance, and attendance. The rate of absenteeism due to health complications was noted. RESULTS: All healthy children were able to attend school (p<0.0001), while 33% of children with JIA were unable to attend school due to their condition. The students with JIA who were able to attend school were absent much more often than controls (63% compared to 20%), with a highly significant p value (p<0.0001). Slightly less than half of the JIA patients (48.5%) failed in their schooling. In univariate analysis, there was an association between absenteeism and tender joints (p=0.02), disease activity score (DAS28) (p=0.007), Childhood Health Assessment Questionnaire (CHAQ) (p=0.01), and erythrocyte sedimentation rate (ESR) (p=0.03). In multivariate analysis, the only association persisted between DAS28 and absenteeism. CONCLUSIONS: Our study suggested that the schooling of children with JIA was negatively impacted due to the disorder. More studies, with a larger sample of children, are needed to confirm our findings.