Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling
<p dir="ltr">Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (<i>MEFV)</i> gene. Despite a typical clinical expression, many patients have either a single...
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| مؤلفون آخرون: | , , , , , , , , , |
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2020
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| _version_ | 1864513555823329280 |
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| author | Meenakshi Umar (492911) |
| author2 | Andre Megarbane (3485465) Jingxuan Shan (4711089) Najeeb Syed (12561967) Eliane Chouery (558481) Elbay Aliyev (14056972) Puthen Jithesh (6561377) Ramzi Temanni (671528) Issam Mansour (14779396) Lotfi Chouchane (61840) Aouatef Ismail Chouchane (14779399) |
| author2_role | author author author author author author author author author author |
| author_facet | Meenakshi Umar (492911) Andre Megarbane (3485465) Jingxuan Shan (4711089) Najeeb Syed (12561967) Eliane Chouery (558481) Elbay Aliyev (14056972) Puthen Jithesh (6561377) Ramzi Temanni (671528) Issam Mansour (14779396) Lotfi Chouchane (61840) Aouatef Ismail Chouchane (14779399) |
| author_role | author |
| dc.creator.none.fl_str_mv | Meenakshi Umar (492911) Andre Megarbane (3485465) Jingxuan Shan (4711089) Najeeb Syed (12561967) Eliane Chouery (558481) Elbay Aliyev (14056972) Puthen Jithesh (6561377) Ramzi Temanni (671528) Issam Mansour (14779396) Lotfi Chouchane (61840) Aouatef Ismail Chouchane (14779399) |
| dc.date.none.fl_str_mv | 2020-08-27T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1111/jcmm.15701 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genome_sequencing_unveils_mutational_landscape_of_the_familial_Mediterranean_fever_Potential_implications_of_IL33_ST2_signalling/22258543 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Familial Mediterranean Fever IL1RL1 MEFV Whole Genome Sequencing |
| dc.title.none.fl_str_mv | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (<i>MEFV)</i> gene. Despite a typical clinical expression, many patients have either a single or no mutation in <i>MEFV</i>. The current work is aimed to revisit the genetic landscape of FMF disease using high-coverage whole genome sequencing. In atypical patients (carrying a single or no mutation in <i>MEFV</i>), we revealed many rare variants in genes associated with auto-inflammatory disorders, and more interestingly, we discovered a novel variant ( a 2.1-Kb deletion) in exon 11 of <i>IL1RL1</i> gene, present only in patients. To validate and screen this patient-specific variant, a tandem of allele-specific PCR and quantitative real-time PCR was performed in 184 FMF patients and 218 healthy controls and we demonstrated that the novel deletion was absent in controls and was present in more than 19% of patients. This study sheds more light on the mutational landscape of FMF. Our discovery of a disease-specific variant in <i>IL1RL1</i> gene may constitute a novel genetic marker for FMF. This finding suggesting a potential role of the IL33/ST2 signalling in the disease pathogenicity highlights a new paradigm in FMF pathophysiology.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.15701" target="_blank">http://dx.doi.org/10.1111/jcmm.15701</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ed7a27bfddff580f29a824f96e795729 |
| identifier_str_mv | 10.1111/jcmm.15701 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22258543 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signallingMeenakshi Umar (492911)Andre Megarbane (3485465)Jingxuan Shan (4711089)Najeeb Syed (12561967)Eliane Chouery (558481)Elbay Aliyev (14056972)Puthen Jithesh (6561377)Ramzi Temanni (671528)Issam Mansour (14779396)Lotfi Chouchane (61840)Aouatef Ismail Chouchane (14779399)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesFamilial Mediterranean FeverIL1RL1MEFVWhole Genome Sequencing<p dir="ltr">Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (<i>MEFV)</i> gene. Despite a typical clinical expression, many patients have either a single or no mutation in <i>MEFV</i>. The current work is aimed to revisit the genetic landscape of FMF disease using high-coverage whole genome sequencing. In atypical patients (carrying a single or no mutation in <i>MEFV</i>), we revealed many rare variants in genes associated with auto-inflammatory disorders, and more interestingly, we discovered a novel variant ( a 2.1-Kb deletion) in exon 11 of <i>IL1RL1</i> gene, present only in patients. To validate and screen this patient-specific variant, a tandem of allele-specific PCR and quantitative real-time PCR was performed in 184 FMF patients and 218 healthy controls and we demonstrated that the novel deletion was absent in controls and was present in more than 19% of patients. This study sheds more light on the mutational landscape of FMF. Our discovery of a disease-specific variant in <i>IL1RL1</i> gene may constitute a novel genetic marker for FMF. This finding suggesting a potential role of the IL33/ST2 signalling in the disease pathogenicity highlights a new paradigm in FMF pathophysiology.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.15701" target="_blank">http://dx.doi.org/10.1111/jcmm.15701</a></p>2020-08-27T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1111/jcmm.15701https://figshare.com/articles/journal_contribution/Genome_sequencing_unveils_mutational_landscape_of_the_familial_Mediterranean_fever_Potential_implications_of_IL33_ST2_signalling/22258543CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/222585432020-08-27T06:00:00Z |
| spellingShingle | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling Meenakshi Umar (492911) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Familial Mediterranean Fever IL1RL1 MEFV Whole Genome Sequencing |
| status_str | publishedVersion |
| title | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| title_full | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| title_fullStr | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| title_full_unstemmed | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| title_short | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| title_sort | Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Familial Mediterranean Fever IL1RL1 MEFV Whole Genome Sequencing |