Genetic panel screening in patients with clinically unclassified systemic autoinflammatory diseases

Demir, Ferhat; Doğan, Özlem Akgün; Demirkol, Yasemin Kendir; Tekkuş, Kübra Ermiş; Canbek, Sezin; Karadağ, Şerife Gül; Sönmez, Hafize Emine; Ayaz, Nuray Aktay; Doganay, Levent; Sözeri, Betül

doi:10.1007/s10067-020-05108-1

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…This rate supports other studies focusing on the genetic diagnosis of AID [5,13,[36][37][38][39][40][41]. Cohorts of equal size [5,13,36] and larger cohorts [41] were both evaluated in these studies, and some only included pediatric patients [12,39,42,43], while others also included adults [36-38, 41, 44, 45]. A higher positive yield was reported in studies with a more selective choice in the patient cohort, e.g.…”

Section: Discussionsupporting

confidence: 84%

“…In addition, we identified in 43.2% VUS, which could become clinically relevant in the future. This rate supports other studies focusing on the genetic diagnosis of AID [5,13,[36][37][38][39][40][41]. Cohorts of equal size [5,13,36] and larger cohorts [41] were both evaluated in these studies, and some only included pediatric patients [12,39,42,43], while others also included adults [36-38, 41, 44, 45].…”

Section: Discussionsupporting

confidence: 83%

“…a diagnostic yield of 36% was observed in cohorts with a high rate of consanguinity [43]. Studies focusing on unclassified SAIDs usually show low diagnostic rates as published by Demir et al [39]. The term "unclassified SAIDs" has been used to describe patients who do not meet the clinical diagnostic criteria for an AID or have clinical findings for more than one AID.…”

Section: Discussionmentioning

confidence: 99%

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Genetics in inborn errors of immunity: pediatric autoinflammatory phenotypes and the underlying genetic causes in 125 families

Poker¹,

Hardenberg

Hofmann³

et al. 2022

Preprint

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Monogenic autoinflammatory diseases (AID) encompass a growing group of inborn errors in the innate immune system causing unprovoked or exaggerated systemic inflammation. Diagnosis of monogenic AID requires an accurate description of the patients´ phenotype and the identification of highly penetrant genetic variants in single genes is pivotal. In a routine genetic diagnostic setting, we performed whole exome sequencing (WES) of 125 pediatric patients with suspected monogenic AID. Datasets were analyzed in a step-wise approach to identify the most feasible diagnostic strategy: First, we analyzed a virtual gene panel including 13 genes associated with known AID and, if no genetic diagnosis could be established, followed by the analysis of a virtual panel including 420 genes published by the International Union of Immunological Societies associated with all known inborn error of immunity (IEI). Subsequently WES data were analyzed without pre-filtering for known AID/IEI genes. Analyzing 13 genes yielded a definite diagnosis in 16.0% (n=20). The diagnostic yield was increased by analyzing 420 genes to 21.8% (n=26). Importantly, expanding the analysis to WES data did not increase the diagnostic yield in our cohort, neither in single WES analysis nor in trio-WES analysis. The study highlights that analyzing virtual gene panels based on WES that include the majority of known genes causing AID or differential diagnosis can rapidly confirm the diagnosis for a large number of pediatric patients. WES data or trio-WES data analysis as a first-tier diagnostic analysis in patients with suspected monogenic AID is of minor use.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetics in inborn errors of immunity: pediatric autoinflammatory phenotypes and the underlying genetic causes in 125 families

Poker¹,

Hardenberg

Hofmann³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The larger cohorts of patients came from the international Eurofever registry, Japan and Middle East [ 16 , 19 , 21 ]. The median ages at the symptoms onset and patient enrollment are 13 (±13) and 25 (±18) years, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The median ages at the symptoms onset and patient enrollment are 13 (±13) and 25 (±18) years, respectively. In the four pediatric studies, the median diagnosis delay was 35 months (range 13–78) [ 5 , 19 , 22 , 23 ]. Males are 42% of the total.…”

Section: Resultsmentioning

confidence: 99%

Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers

Papa

Penco

Volpi

et al. 2021

JCM

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Syndrome of undifferentiated recurrent fever (SURF) is a heterogeneous group of autoinflammatory diseases (AID) characterized by self-limiting episodes of systemic inflammation without a confirmed molecular diagnosis, not fulfilling the criteria for periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. In this review, we focused on the studies enrolling patients suspected of AID and genotyped them with next generation sequencing technologies in order to describe the clinical manifestations and treatment response of published cohorts of patients with SURF. We also propose a preliminary set of indications for the clinical suspicion of SURF that could help in everyday clinical practice.

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Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases

et al. 2020

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Genetic panel screening in patients with clinically unclassified systemic autoinflammatory diseases

Cited by 14 publications

References 29 publications

Genetics in inborn errors of immunity: pediatric autoinflammatory phenotypes and the underlying genetic causes in 125 families

Genetics in inborn errors of immunity: pediatric autoinflammatory phenotypes and the underlying genetic causes in 125 families

Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers

Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases

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