Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation
Background: Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome inherited as an autosomal recessive pattern; nonetheless, patients with symptomatic heterozygous variants exist. This study aimed to review children with genetically-proven FMF, to describe their mutation maps and...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Pediatrics and Neonatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957222002170 |
| _version_ | 1797857689263407104 |
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| author | Eyad Altamimi Dua` N. Samara Dima Bani Issa Saied Jaradat Wail Hayajneh |
| author_facet | Eyad Altamimi Dua` N. Samara Dima Bani Issa Saied Jaradat Wail Hayajneh |
| author_sort | Eyad Altamimi |
| collection | DOAJ |
| description | Background: Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome inherited as an autosomal recessive pattern; nonetheless, patients with symptomatic heterozygous variants exist. This study aimed to review children with genetically-proven FMF, to describe their mutation maps and clinical characteristics, and to explore the genotype–phenotype correlation. Methods: Medical charts of pediatric FMF patients who were diagnosed by both genetic mutation and clinical criteria and followed up at our hospital were reviewed. Demographic and clinical data, results of MEFV genetic testing, procedures, concomitant medical conditions, disease severity, and treatment response were recorded and analyzed. Results: A total of 132 patients (71 females [54%]) were included in the final analysis. The average ages at presentation and diagnosis were 6.2 ± 3.1 and 7.6 ± 4.4 years, respectively. The most common clinical features were abdominal pain (n = 120, 91%), fever (n = 97, 73.5%), and arthritis (n = 75, 56.2%). Gastrointestinal endoscopy was the most frequently reported procedure (n = 27, 20.45%). The most common mutation was R202Q (n = 71, 53.8%), followed by E148Q (n = 36, 27.3%), M694V (n = 30, 22.7%), and V726A (n = 22, 16.7%). Two rare variants with potential pathogenicity were identified—namely, c.-15 and c.-330. A novel MEFV mutation (p. Lys629 Met) was noted. Abdominal pain, arthritis, arthralgia, and skin rashes were more common with the R202Q mutation. Patients with compound heterozygous mutations showed a higher rate of abdominal pain (94.1%) and exhibited the best response to colchicine (67.6%). Patients with complex alleles had the highest rate of fever (80%) and arthritis/arthralgia (70%). Conclusion: FMF is endemic in Jordan. Genetic testing is important in FMF evaluation; however, the genotype–phenotype correlation needs further study. The R202Q mutation is possibly pathogenic and is associated with the manifestation of the full spectrum of FMF features; hence, it needs to be considered in the diagnosis of FMF patients in Jordan. |
| first_indexed | 2024-04-09T21:00:51Z |
| format | Article |
| id | doaj.art-7a7997b35eaa4e12b8a3063d8d47aed5 |
| institution | Directory Open Access Journal |
| issn | 1875-9572 |
| language | English |
| last_indexed | 2024-04-09T21:00:51Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj.art-7a7997b35eaa4e12b8a3063d8d47aed52023-03-29T09:25:32ZengElsevierPediatrics and Neonatology1875-95722023-03-01642183191Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutationEyad Altamimi0Dua` N. Samara1Dima Bani Issa2Saied Jaradat3Wail Hayajneh4Pediatric Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; Corresponding author. Pediatric Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan, 3030, 22110.Pediatric Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid, JordanPediatric Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid, JordanPrincess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid JordanSchool of Medicine, Saint Louis University, Missouri USA; School of Medicine, Jordan University of Science and Technology, Irbid, JordanBackground: Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome inherited as an autosomal recessive pattern; nonetheless, patients with symptomatic heterozygous variants exist. This study aimed to review children with genetically-proven FMF, to describe their mutation maps and clinical characteristics, and to explore the genotype–phenotype correlation. Methods: Medical charts of pediatric FMF patients who were diagnosed by both genetic mutation and clinical criteria and followed up at our hospital were reviewed. Demographic and clinical data, results of MEFV genetic testing, procedures, concomitant medical conditions, disease severity, and treatment response were recorded and analyzed. Results: A total of 132 patients (71 females [54%]) were included in the final analysis. The average ages at presentation and diagnosis were 6.2 ± 3.1 and 7.6 ± 4.4 years, respectively. The most common clinical features were abdominal pain (n = 120, 91%), fever (n = 97, 73.5%), and arthritis (n = 75, 56.2%). Gastrointestinal endoscopy was the most frequently reported procedure (n = 27, 20.45%). The most common mutation was R202Q (n = 71, 53.8%), followed by E148Q (n = 36, 27.3%), M694V (n = 30, 22.7%), and V726A (n = 22, 16.7%). Two rare variants with potential pathogenicity were identified—namely, c.-15 and c.-330. A novel MEFV mutation (p. Lys629 Met) was noted. Abdominal pain, arthritis, arthralgia, and skin rashes were more common with the R202Q mutation. Patients with compound heterozygous mutations showed a higher rate of abdominal pain (94.1%) and exhibited the best response to colchicine (67.6%). Patients with complex alleles had the highest rate of fever (80%) and arthritis/arthralgia (70%). Conclusion: FMF is endemic in Jordan. Genetic testing is important in FMF evaluation; however, the genotype–phenotype correlation needs further study. The R202Q mutation is possibly pathogenic and is associated with the manifestation of the full spectrum of FMF features; hence, it needs to be considered in the diagnosis of FMF patients in Jordan.http://www.sciencedirect.com/science/article/pii/S1875957222002170colchicinefamilial mediterranean feverMEFVR202Qrenal insufficiency |
| spellingShingle | Eyad Altamimi Dua` N. Samara Dima Bani Issa Saied Jaradat Wail Hayajneh Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation Pediatrics and Neonatology colchicine familial mediterranean fever MEFV R202Q renal insufficiency |
| title | Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation |
| title_full | Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation |
| title_fullStr | Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation |
| title_full_unstemmed | Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation |
| title_short | Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation |
| title_sort | genotype phenotype correlation in jordanian children with genetically proven familial mediterranean fever the effect of r202q mutation |
| topic | colchicine familial mediterranean fever MEFV R202Q renal insufficiency |
| url | http://www.sciencedirect.com/science/article/pii/S1875957222002170 |
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