Patient management and the association of less common familial Mediterranean fever symptoms with other disorders

Moradian, Mike M.; Sarkisian, Tamara; Amaryan, Gayane; Hayrapetyan, Hasmik; Yeghiazaryan, Anna; Davidian, N R; Avanesian, Nare

doi:10.1038/gim.2013.112

Cited by 11 publications

(5 citation statements)

References 20 publications

(15 reference statements)

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“…TNFR2 signaling is protective against colitis and arthritis in Mefv V726A/V726A mice. Serosal inflammation, including inflammation in the colon and joints, has been observed in both FMF patients (50) and the murine model of FMF (5). We have previously shown that IL-1β protects against serosal tissue inflammation in Mefv V726A/V726A mice (10).…”

Section: Tnf Promotes Pyrin Expression and Inflammasome Activationmentioning

confidence: 99%

TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy

Sharma¹,

Malik²,

Guy³

et al. 2018

Journal of Clinical Investigation

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Section: Tnf Promotes Pyrin Expression and Inflammasome Activationmentioning

confidence: 99%

TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy

Sharma¹,

Malik²,

Guy³

et al. 2018

Journal of Clinical Investigation

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“…3,5,6 With an estimated 20%, the overall MEFV carrier rate in the Armenian population is extremely high, resulting in an FMF prevalence of approximately 3%. 7,8 In general, FMF diagnosis is based on clinical findings, which can be backed up but never replaced by genetic testing. 9 Moreover, diagnosing FMF may be extremely difficult in individuals with nonspecific symptoms, with late-onset disease, or with an absence of family history.…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic heterogeneity in a large cohort of Armenian patients with late-onset familial Mediterranean fever

Kriegshäuser

Enko

Hayrapetyan

et al. 2018

Genetics in Medicine

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PurposeThis work aimed at investigating demographic, clinical, and genetic characteristics of individuals experiencing their first familial Mediterranean fever (FMF) attack at age ≥40 years in a very large cohort of Armenian FMF patients.MethodsIn total, 10,370 Armenian patients diagnosed with FMF based on the Tel Hashomer criteria and carrying at least one MEFV mutant allele were included in this study.ResultsA total of 354 (3.40%) patients had late-onset FMF. Of these, 194 (54.80%) were female and 160 (45.20%) were male. The following genotypes were significantly associated with the late-onset variant: M680I/E148Q (P = 0.004), M694V/E148Q (P< 0.001), and V726A/V726A (P< 0.001). Of note, 12/354 (3.40%) patients were found to be homozygous for the M694V mutation. Individuals with late-onset FMF had a milder disease phenotype presenting significantly less frequent fever, skin manifestation, and chest pain compared to individuals with a disease onset before 40 years of age. Abdominal pain was found more often in the late-onset FMF group, whereas arthritis, proteinuria, and amyloidosis did not differ significantly between the two groups.ConclusionOur data suggest that late-onset FMF is more prevalent in women and is of greater clinical as well as genetic heterogeneity than previously reported.GENETICS in MEDICINE advance online publication, 15 March 2018; doi:10.1038/gim.2018.46.

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“…Noting the possibility of other variants contributing to disease heterogeneity and severity, analysis of RNA continued and identified a pathogenic missense SNV in MEFV (HGNC:6998) along with an intron retention event. Although a second variant was not identified in MEFV , the highly penetrant M680I mutation has been previously observed in symptomatic carriers of familial Mediterranean fever (FMF, OMIM 249100) [ 70 , 71 , 72 ]. Whether or not a carrier with this variant will be symptomatic does not appear consistent within families, suggesting low penetrance and variable expressivity, possibly due to the presence of modifier mutations in other genes.…”

Section: Resultsmentioning

confidence: 99%

Targeted RNAseq Improves Clinical Diagnosis of Very Early-Onset Pediatric Immune Dysregulation

Berger

Arafat

Chandrakasan

et al. 2022

JPM

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Despite increased use of whole exome sequencing (WES) for the clinical analysis of rare disease, overall diagnostic yield for most disorders hovers around 30%. Previous studies of mRNA have succeeded in increasing diagnoses for clearly defined disorders of monogenic inheritance. We asked if targeted RNA sequencing could provide similar benefits for primary immunodeficiencies (PIDs) and very early-onset inflammatory bowel disease (VEOIBD), both of which are difficult to diagnose due to high heterogeneity and variable severity. We performed targeted RNA sequencing of a panel of 260 immune-related genes for a cohort of 13 patients (seven suspected PID cases and six VEOIBD) and analyzed variants, splicing, and exon usage. Exonic variants were identified in seven cases, some of which had been previously prioritized by exome sequencing. For four cases, allele specific expression or lack thereof provided additional insights into possible disease mechanisms. In addition, we identified five instances of aberrant splicing associated with four variants. Three of these variants had been previously classified as benign in ClinVar based on population frequency. Digenic or oligogenic inheritance is suggested for at least two patients. In addition to validating the use of targeted RNA sequencing, our results show that rare disease research will benefit from incorporating contributing genetic factors into the diagnostic approach.

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Patient management and the association of less common familial Mediterranean fever symptoms with other disorders

Cited by 11 publications

References 20 publications

TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy

TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy

Clinical and genetic heterogeneity in a large cohort of Armenian patients with late-onset familial Mediterranean fever

Targeted RNAseq Improves Clinical Diagnosis of Very Early-Onset Pediatric Immune Dysregulation

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