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The role of MEFV gene mutations in Multiple Sclerosis susceptibility

Published:September 09, 2010DOI:https://doi.org/10.1016/j.jns.2010.08.018
      With great interest and pleasure, we have read the article by Unal et al. [

      Unal A, Dursun A, Emre U, Tascilar NF, Ankarali H. Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: Is it a susceptibility gene? J Neurol Sci 2010 May 17. [Epub ahead of print].

      ] and have some comments about the final results and discussion. In brief, Unal et al. evaluated common mutations (E148Q, M680I, M694V, M694I and V726A) in the Mediterranean fever gene, MEFV gene, among MS patients and declared significant association between MEFV gene mutation and multiple sclerosis. With all sincerity, we think that the following points need to be more illuminated and explained:
      • 1.
        In a study performed by Tchernitchko et al. [
        • Tchernitchko D.
        • Legendre M.
        • Cazeneuve C.
        • Delahaye A.
        • Niel F.
        • Amselem S.
        The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever.
        ], it has been shown that the E148Q MEFV allele is just a benign polymorphism and is not involved in Familial Mediterranean Fever (FMF). Supporting this study, 2 disease free individuals were identified in another investigation being homozygous for E148Q mutation [
        • Ben-Chetrit E.
        • Lerer I.
        • Malamud E.
        • Domingo C.
        • Abeliovich D.
        The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant?.
        ]. These studies may suggest a weak influence of E148Q mutation on MEFV gene function. Thus the role of this polymorphism is controversial in FMF and much more in MS.
      • 2.
        In the recent research by Unal et al. [

        Unal A, Dursun A, Emre U, Tascilar NF, Ankarali H. Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: Is it a susceptibility gene? J Neurol Sci 2010 May 17. [Epub ahead of print].

        ], approximately most of the MS patients (80%) carrying MEFV gene mutations have only one copy of each mutation. As we know two copies of these mutations can change the gene function more significantly so homozygote patients are more considerable. However, the rate of MS patients which are homozygous for these polymorphisms is very low in this study.
      • 3.
        While it is evidently known that FMF is a familial recessive disease, no family history of FMF was reported for the MS patients evaluated in the investigation by Unal et al. Furthermore, in a study assessing MEFV gene mutations in MS patients, no evidence of association with MS was observed for these variants [
        • Shinar Y.
        • Livneh A.
        • Villa Y.
        • Pinhasov A.
        • Zeitoun I.
        • Kogan A.
        • et al.
        Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients.
        ].
      • 4.
        Several studies have indicated a high incidence of FMF among the Arab populations [
        • Belmahi L.
        • Sefiani A.
        • Fouveau C.
        • Feingold J.
        • Delpech M.
        • Grateau G.
        • et al.
        Prevalence and distribution of MEFV mutations among Arabs from the Maghreb patients suffering from familial Mediterranean fever.
        ,
        • El-Shanti H.
        • Majeed H.A.
        • El-Khateeb M.
        Familial mediterranean fever in Arabs.
        ,
        • Majeed H.A.
        • El-Khateeb M.
        • El-Shanti H.
        • Rabaiha Z.A.
        • Tayeh M.
        • Najib D.
        The spectrum of familial Mediterranean fever gene mutations in Arabs: report of a large series.
        ]. On the other hand, the prevalence of MS among the Arabs appears to be lower than other countries [
        • Benamer H.T.
        • Ahmed E.S.
        • Al-Din A.S.
        • Grosset D.G.
        Frequency and clinical patterns of multiple sclerosis in Arab countries: a systematic review.
        ]. Regarding these evidences, MEFV gene, the main factor causing FMF disease, could not be considered as a susceptible gene in MS pathogenesis.
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      References

      1. Unal A, Dursun A, Emre U, Tascilar NF, Ankarali H. Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: Is it a susceptibility gene? J Neurol Sci 2010 May 17. [Epub ahead of print].

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        • Legendre M.
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        • Delahaye A.
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        The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever.
        Hum Mutat. 2003; 22: 339-340
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        • Lerer I.
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        • Domingo C.
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        The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant?.
        Hum Mutat. 2000; 15: 385-386
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        • Livneh A.
        • Villa Y.
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        Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients.
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