Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics
Authors: Ridvan Mercan
Hilmi Tozkir
Esra Bozgeyik
Ahmet Arslan
Journal: Genomics (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FMF; Fever panel; MEFV; Next-generation sequencing.
Affiliations: Tekirdag Namik Kemal University, Faculty of Medicine, Department of Medical Biology, Tekirdag, Turkey. Electronic address: ., Tekirdag Namik Kemal University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Tekirdag, Turkey., Tekirdag Namik Kemal University, Faculty of Medicine, Department of Medical Genetics, Tekirdag, Turkey.

Abstract:  Familial Mediterranean Fever (FMF) is a hereditary fever syndrome that primarily affects Mediterranean populations. For the study, total number of 182 patients with FMF disease were enrolled and screening of a panel of genes , called "fever panel" which comprises 17 genes, was performed. The most common mutations in MEFV gene were homozygous M694V missense mutation (4.3%) and R202Q missense mutation (4.9%). The most common heterozygous mutations were R202Q (26.5%), M694V (25.9%) and E148Q (11.9%). Compound heterozygous and homozygous mutations were also detected. Also, different types of mutations were identified in NOD2, CARD14, NLRP12, NLRP3, NLRP7, IL1RN, LPIN2, TNFRSF1A, MVK and PSTPIP1 genes. Two novel missense variations in the MEFV gene, Gln34Pro and Ile247Val, which have not been previously reported in the databases, were identified. Also, Thr91Ile missense variation in the NOD2 gene, Gly461Cys missense variation in NLRP3 and Tyr732Stop nonsense variation in LPIN2 were firstly identified. The results of the current study suggest that in addition to the MEFV gene which has an important roles in FMF, molecular screening of other genes related to other autoinflammatory diseases might provide support in suspected cases and provide detailed information about the course of the disease. 

Retracted: No

PubPeer comments:
 I found several issues in this article. 1. In statistical analysis heading, the authors declared to used Chi-square and Pearson correlation tests for the analysis of categorical variables and to determine the relationship between the variables, respectively. However, according to the paper, they do not have a categorical variable for the Chi-square test or they did not express a correlation finding in the results. So, how and where did the authors use these tests? 2. Some sentences overlap with already published articles and the authors did not cite those papers. For example, the sentence u201cFMF is characterized by recurrent fever, peritonitis, pleuritis, arthritis and erysipelas-like skin lesions (1,2u201d) is similar to following sentence from Familial Mediterranean fever (lancer seminars). u201cIt is characterised by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease.u201d 3. The sentence u201cAlthough FMF is an autosomal recessive disease, individuals with heterozygous mutations have also shown to exhibit the classic symptoms of the disease [3]u201d is same with the sentence u201cAlthough this is an autosomal recessive disease, heterozygous individuals have also been shown to exhibit classical disease-related symptomsu201d from The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T), J Clinic Med. However, the authors did not cite this paper. 4. The other sentence u201cAnother finding that supports the diagnosis is the increase in acute phase reactants, which are known to increase in inflammatory events during attack periods. C-reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen and leukocyte count increase in attacksu201d is 90% same with the sentence from Braz J Med Biol Res. 2013 Oct; 46(10): 904u2013908 u201cAnother finding that supports diagnosis is a rise in acute-phase reactants, known to increase in acute inflammatory events in attack periods. C-reactive protein (CRP), sedimentation, fibrinogen, and white blood cell counts rise during attacks.u201d And the authors did not cite this paper.u201d This could be considered as plagiarism. 5. The sentence at the beginning of discussion u201cAlthough the clinical symptoms and course of the disease is still the cornerstone for the diagnosis of FMF, genetic confirmation of this condition helps to make differential diagnosis, especially in suspicious Casesu201d is %85 similar to the sentence from Med Arch. 2015 Dec; 69(6): 417u2013420. u201cAlthough clinical symptoms and the course of the illness are still the cornerstones of diagnosing FMF, molecular confirmation can help make the diagnosis earlier in suspected cases (3)u201d. And the authors did not cite this paper. These issues could be problematic. Especially overlaps without citations should be fixed somehow or removed. ,