Familial mediterranean fever pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Familial Mediterranean fever}} | {{Familial Mediterranean fever}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} | ||
==Overview== | ==Overview== | ||
==Pathophysiology== | ==Pathophysiology== | ||
*Approximately, all cases are due to a mutation in the MEFV gene, which codes for a protein called pyrin or marenostrin (from the original name of the Mediterranean sea, Marenostrum).<ref name="pmid10807793">{{cite journal |vauthors=Centola M, Wood G, Frucht DM, Galon J, Aringer M, Farrell C, Kingma DW, Horwitz ME, Mansfield E, Holland SM, O'Shea JJ, Rosenberg HF, Malech HL, Kastner DL |title=The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators |journal=Blood |volume=95 |issue=10 |pages=3223–31 |date=May 2000 |pmid=10807793 |doi= |url=}}</ref> | *Approximately, all cases are due to a [[mutation]] in the [[MEFV]] [[gene]], which codes for a [[protein]] called pyrin or marenostrin (from the original name of the Mediterranean sea, Marenostrum).<ref name="pmid10807793">{{cite journal |vauthors=Centola M, Wood G, Frucht DM, Galon J, Aringer M, Farrell C, Kingma DW, Horwitz ME, Mansfield E, Holland SM, O'Shea JJ, Rosenberg HF, Malech HL, Kastner DL |title=The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators |journal=Blood |volume=95 |issue=10 |pages=3223–31 |date=May 2000 |pmid=10807793 |doi= |url=}}</ref> | ||
*The function of pyrin has not been completely elucidated, but it appears to be a suppressor of the activation of [[caspase 1]], the [[enzyme]] that stimulates production of [[IL-1|interleukin 1β]], a [[cytokine]] central to the process of [[inflammation]]. It is not conclusively known what exactly sets off the attacks, and why overproduction of IL-1 would lead to particular symptoms in particular organs (e.g. joints or the peritoneal cavity). | *The function of pyrin has not been completely elucidated, but it appears to be a suppressor of the activation of [[caspase 1]], the [[enzyme]] that stimulates production of [[IL-1|interleukin 1β]], a [[cytokine]] central to the process of [[inflammation]]. It is not conclusively known what exactly sets off the attacks, and why overproduction of IL-1 would lead to particular symptoms in particular organs (e.g. joints or the peritoneal cavity). | ||
===Genetics=== | ===Genetics=== | ||
*The [[MEFV]] [[gene]] is located on the short arm of [[chromosome 16 (human)|chromosome 16]] (16p13) which consists of 10 exons.<ref name="pmid9288094">{{cite journal |vauthors= |title=A candidate gene for familial Mediterranean fever |journal=Nat. Genet. |volume=17 |issue=1 |pages=25–31 |date=September 1997 |pmid=9288094 |doi=10.1038/ng0997-25 |url=}}</ref> | *The [[MEFV]] [[gene]] is located on the short arm of [[chromosome 16 (human)|chromosome 16]] (16p13) which consists of 10 [[exons]].<ref name="pmid9288094">{{cite journal |vauthors= |title=A candidate gene for familial Mediterranean fever |journal=Nat. Genet. |volume=17 |issue=1 |pages=25–31 |date=September 1997 |pmid=9288094 |doi=10.1038/ng0997-25 |url=}}</ref> | ||
*The majority of mutations occur in exon 10.<ref name="pmid11464238">{{cite journal |vauthors=Touitou I |title=The spectrum of Familial Mediterranean Fever (FMF) mutations |journal=Eur. J. Hum. Genet. |volume=9 |issue=7 |pages=473–83 |date=July 2001 |pmid=11464238 |doi=10.1038/sj.ejhg.5200658 |url=}}</ref> | *The majority of [[mutations]] occur in [[exon]] 10.<ref name="pmid11464238">{{cite journal |vauthors=Touitou I |title=The spectrum of Familial Mediterranean Fever (FMF) mutations |journal=Eur. J. Hum. Genet. |volume=9 |issue=7 |pages=473–83 |date=July 2001 |pmid=11464238 |doi=10.1038/sj.ejhg.5200658 |url=}}</ref> | ||
*The E148Q, M680I, M694V, M694I, and V726A mutations have been observed to be responsible for more than 80% of FMF cases in the Middle Eastern region. | *The E148Q, M680I, M694V, M694I, and V726A [[mutations]] have been observed to be responsible for more than 80% of [[FMF]] cases in the Middle Eastern region. | ||
*The disease inherits in an [[autosomal recessive]] mode. However, there is an increasing number of data reporting the autosomal dominant inheritance.<ref name="pmid10787449">{{cite journal |vauthors=Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A, Soytürk M, Akar S, Pepys MB, Tunca M, Hawkins PN |title=The genetic basis of autosomal dominant familial Mediterranean fever |journal=QJM |volume=93 |issue=4 |pages=217–21 |date=April 2000 |pmid=10787449 |doi=10.1093/qjmed/93.4.217 |url=}}</ref><ref name="pmid14679589">{{cite journal |vauthors=Aldea A, Campistol JM, Arostegui JI, Rius J, Maso M, Vives J, Yagüe J |title=A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder? |journal=Am. J. Med. Genet. A |volume=124A |issue=1 |pages=67–73 |date=January 2004 |pmid=14679589 |doi=10.1002/ajmg.a.20296 |url=}}</ref> | *The [[disease]] inherits in an [[autosomal recessive]] mode. However, there is an increasing number of data reporting the [[autosomal dominant]] [[inheritance]].<ref name="pmid10787449">{{cite journal |vauthors=Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A, Soytürk M, Akar S, Pepys MB, Tunca M, Hawkins PN |title=The genetic basis of autosomal dominant familial Mediterranean fever |journal=QJM |volume=93 |issue=4 |pages=217–21 |date=April 2000 |pmid=10787449 |doi=10.1093/qjmed/93.4.217 |url=}}</ref><ref name="pmid14679589">{{cite journal |vauthors=Aldea A, Campistol JM, Arostegui JI, Rius J, Maso M, Vives J, Yagüe J |title=A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder? |journal=Am. J. Med. Genet. A |volume=124A |issue=1 |pages=67–73 |date=January 2004 |pmid=14679589 |doi=10.1002/ajmg.a.20296 |url=}}</ref> | ||
==Associated Conditions== | ==Associated Conditions== | ||
Conditions associated with Familial Mediterranean fever include: | [[Conditions]] associated with [[Familial mediterranean fever|Familial Mediterranean fever]] include: | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Revision as of 17:23, 21 May 2019
Template:Familial Mediterranean fever
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
- Approximately, all cases are due to a mutation in the MEFV gene, which codes for a protein called pyrin or marenostrin (from the original name of the Mediterranean sea, Marenostrum).[1]
- The function of pyrin has not been completely elucidated, but it appears to be a suppressor of the activation of caspase 1, the enzyme that stimulates production of interleukin 1β, a cytokine central to the process of inflammation. It is not conclusively known what exactly sets off the attacks, and why overproduction of IL-1 would lead to particular symptoms in particular organs (e.g. joints or the peritoneal cavity).
Genetics
- The MEFV gene is located on the short arm of chromosome 16 (16p13) which consists of 10 exons.[2]
- The majority of mutations occur in exon 10.[3]
- The E148Q, M680I, M694V, M694I, and V726A mutations have been observed to be responsible for more than 80% of FMF cases in the Middle Eastern region.
- The disease inherits in an autosomal recessive mode. However, there is an increasing number of data reporting the autosomal dominant inheritance.[4][5]
Associated Conditions
Conditions associated with Familial Mediterranean fever include:
References
- ↑ Centola M, Wood G, Frucht DM, Galon J, Aringer M, Farrell C, Kingma DW, Horwitz ME, Mansfield E, Holland SM, O'Shea JJ, Rosenberg HF, Malech HL, Kastner DL (May 2000). "The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators". Blood. 95 (10): 3223–31. PMID 10807793.
- ↑ "A candidate gene for familial Mediterranean fever". Nat. Genet. 17 (1): 25–31. September 1997. doi:10.1038/ng0997-25. PMID 9288094.
- ↑ Touitou I (July 2001). "The spectrum of Familial Mediterranean Fever (FMF) mutations". Eur. J. Hum. Genet. 9 (7): 473–83. doi:10.1038/sj.ejhg.5200658. PMID 11464238.
- ↑ Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A, Soytürk M, Akar S, Pepys MB, Tunca M, Hawkins PN (April 2000). "The genetic basis of autosomal dominant familial Mediterranean fever". QJM. 93 (4): 217–21. doi:10.1093/qjmed/93.4.217. PMID 10787449.
- ↑ Aldea A, Campistol JM, Arostegui JI, Rius J, Maso M, Vives J, Yagüe J (January 2004). "A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?". Am. J. Med. Genet. A. 124A (1): 67–73. doi:10.1002/ajmg.a.20296. PMID 14679589.