TY - JOUR
T1 - The M694I/M694I genotype
T2 - A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever
AU - Ait-Idir, Djouher
AU - Djerdjouri, Bahia
AU - Bouldjennet, Faiza
AU - Taha, Rowaida Z.
AU - El-Shanti, Hatem
AU - Sari-Hamidou, Rawda
AU - Khellaf, Ghalia
AU - Benmansour, Mustapha
AU - Benabadji, Mohamed
AU - Haddoum, Farid
N1 - Publisher Copyright:
© 2016 Elsevier Masson SAS
PY - 2017/3
Y1 - 2017/3
N2 - Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end- stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end- stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients. (C) 2016 Elsevier Masson SAS. All rights reserved.
AB - Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end- stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end- stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients. (C) 2016 Elsevier Masson SAS. All rights reserved.
KW - Algeria
KW - Familial Mediterranean fever
KW - MEFV gene
KW - Renal AA-amyloidosis
KW - p.M694I
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=hbku_researchportal&SrcAuth=WosAPI&KeyUT=WOS:000398068600001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.ejmg.2016.12.003
DO - 10.1016/j.ejmg.2016.12.003
M3 - Article
C2 - 27956278
SN - 1769-7212
VL - 60
SP - 149
EP - 153
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 3
ER -