Clinical research A study of familial Mediterranean Fever (MEFV) gene mutations in Egyptian children with type 1 diabetes mellitus Ghada Mohammad Anwar a , Hanan M. Fouad b, * , Amal Abd El-Hamid b , Faten Mahmoud c , Noha Musa a , Hala Lotfi a , Nermine Salah a a Pediatric Department, Cairo University, Cairo, Egypt b Pediatric Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt c Chemical Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt article info Article history: Received 10 July 2014 Accepted 19 October 2014 Available online 4 November 2014 Keywords: Type 1 diabetes Familial Mediterranean fever Children MEFV gene mutation abstract Background/Aims: An association of type 1 DM and familial Mediterranean fever (FMF) has been newly reported in the medical literature. The aim of the present work was to investigate frequency of MEFV gene mutations in Egyptian children with type 1 diabetes mellitus. Methods: Forty five children with type 1 DM were screened for Mediterranean Fever (MEFV) gene mutation. Forty one healthy control subjects were included. Identification of FMF gene mutation was done based on polymerase chain reaction (PCR) and reverse hybridization. The assay covers 12 mutations in the FMF gene: E148Q e P369S e F479L e M680I (G/C) e M680I (G/A) e I692del e M694V e M694I e K695ReV726A e A744S and R761H. Results: Among the screened diabetics, the overall frequency of MEFV gene mutations was 42.2% and among the control group it was 34.1% with no significant difference. Fourteen out of 45 diabetic children (31.1%) were heterozygous (E148Q in 7 children, A744S in 3 children, V726A in 2 children, M680I (G/C) in 1 child and P369S in1 child), while 5 children (11.1%) were compound heterozygous (M694V/M694I in 2 children, E148Q/K695R mutations in 1 child, E148Q/M694I in 1 child and E148Q/V726A in 1 child). The control group showed heterozygous mutation in 34.1% of cases (E148Q mutation in 14.6%, V726A in 12.2%, M680I (G/C) in 4.9% and M694V in 2.4%). Conclusion: No significant difference in mutation frequency between diabetic and non-diabetic children. We have high carrier rate of MEFV gene mutations among Egyptian population probably due to high consanguinity. Ó 2014 Elsevier Masson SAS. All rights reserved. 1. Introduction Familial Mediterranean fever (FMF) is an autoinflammatory diseases that is often associated with other autoimmune diseases such as ankylosing spondylitis, rheumatoid arthritis, polyarteritis nodosa (PAN), Behcet, multiple sclerosis (MS), and Systemic Lupus (SLE), Henoch-Schönlein purpura, and Hashimoto’s thyroiditis [Yildiz et al., 2010; Aksu and Keser, 2011; Erten et al., 2013; Ergul et al., 2013]. An association of type 1 DM and FMF has been newly reported in the medical literature [Atabek et al., 2006; Bas ¸ et al., 2009]. FMF is an autosomal recessive disorder and it comprises two phenotypes: FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and rarely, pericarditis and meningitis. FMF type 2 is characterized by amyloidosis as the first clinical mani- festation of FMF in an otherwise asymptomatic individual [Shohat and Halpern, 2011]. In 1997 the gene responsible for FMF, MEFV, was identified [Ritis et al., 2004; FMF International Consortium, 1997]. FMF is due to recessive mutations in the MEFV (for Mediterranean Fever) gene, located on the short arm of the chromosome 16 (16p13.3), consisting of 10 exons and 781 codons [Pras et al., 1992]. The type and combination of the mutations define a severely or weakly expressed phenotype [Ben-Chetrit, 2003; Dodé et al., 2000; Gershoni-Baruch et al., 2002], but, on the other hand, subjects carrying two mutations may not express the disease [Kogan et al., 2001]. Mutations in the pyrin/marenostrin (MEFV) gene have been identified in the majority of FMF patients [Aksentijevich et al., 1999; * Corresponding author. E-mail address: hananminaped@gmail.com (H.M. Fouad). Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg http://dx.doi.org/10.1016/j.ejmg.2014.10.005 1769-7212/Ó 2014 Elsevier Masson SAS. All rights reserved. European Journal of Medical Genetics 58 (2015) 31e34