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. 2020 Nov;41(11):1866-1870.
doi: 10.1002/humu.24090. Epub 2020 Oct 5.

Familial Mediterranean fever: Penetrance of the p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=] genotypes

Ori Eyal  1   2 , Yael Shinar  3 , Mordechai Pras  3   4 , Elon Pras  1   4
Affiliations

Familial Mediterranean fever: Penetrance of the p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=] genotypes

Ori Eyal et al. Hum Mutat. 2020 Nov.

Abstract

The penetrance of the p.[Met694Val];[Met694Val] genotype of pyrin in adult familial Mediterranean fever (FMF) patients is close to 100%. Disease penetrance of the p.[Met694Val];[Glu148Gln] genotype (M694V/E148Q), and the heterozygous p.[Met694Val];[=] genotype is unknown. A difference in the penetrance of the latter two may indicate functionality for the p.Glu148Gln variant. We performed a penetrance estimation study using controls and patients of North African Jewish (NAJ) decent. FMF in this population is highly prevalent and mutation frequencies are well known. The ratio between the calculated frequencies of the three genotypes obtained from the control cohort and the actual frequency obtained from the patient cohort were used to determine the penetrance of p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=]. We found a penetrance of 0.135 and 0.008 for p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=], respectively. Thus, the penetrance of p.[Met694Val];[Glu148Gln] is more than 17 times higher than p.[Met694Val];[=], indicating an active role for p.Glu148Gln when combined with p.Met694Val.

Keywords: E148Q; M694V; familial Mediterranean fever; genotypes; penetrance.

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References

REFERENCES

    1. Aganna, E., Hawkins, P. N., Ozen, S., Pettersson, T., Bybee, A., McKee, S. A., … Besbas, N. (2004). Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis. Genes & Immunity, 5(4), 289-293.
    1. Aydın, F., Çakar, N., Özçakar, Z. B., Uncu, N., Başaran, Ö., Özdel, S., … Yalçınkaya, F. (2019). Clinical features and disease severity of Turkish FMF children carrying E148Q mutation. Journal of Clinical Laboratory Analysis, 33(4), e22852.
    1. Ben-Chetrit, E., Lerer, I., Malamud, E., Domingo, C., & Abeliovich, D. (2000). The E148Q mutation in the MEFV gene: Is it a disease-causing mutation or a sequence variant? Human Mutation, 15(4), 385-386.
    1. Booty, M. G., Chae, J. J., Masters, S. L., Remmers, E. F., Barham, B., Le, J. M., … Aksentijevich, I. (2009). Familial Mediterranean fever with a single MEFV mutation: Where is the second hit? Arthritis and Rheumatism, 60(6), 1851-1861.
    1. Bunker, D., & Gorevic, P. (2012). AA amyloidosis: Mount Sinai experience, 1997-2012. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, 79(6), 749-756.

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