The M694I/M694I genotype

A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever

Djouher Ait-Idir, Bahia Djerdjouri, Faiza Bouldjennet, Rowaida Taha, Hatem El-Shanti, Rawda Sari-Hamidou, Ghalia Khellaf, Mustapha Benmansour, Mohamed Benabadji, Farid Haddoum

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)149-153
Number of pages5
JournalEuropean Journal of Medical Genetics
Volume60
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017

Fingerprint

Familial Mediterranean Fever
Amyloidosis
Genotype
Kidney
Mutation
Chronic Kidney Failure
Fever
Algeria
Genetic Databases
Age of Onset
Gene Frequency
Exons
Alleles

Keywords

  • Algeria
  • Familial Mediterranean fever
  • MEFV gene
  • p.M694I
  • Renal AA-amyloidosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

The M694I/M694I genotype : A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever. / Ait-Idir, Djouher; Djerdjouri, Bahia; Bouldjennet, Faiza; Taha, Rowaida; El-Shanti, Hatem; Sari-Hamidou, Rawda; Khellaf, Ghalia; Benmansour, Mustapha; Benabadji, Mohamed; Haddoum, Farid.

In: European Journal of Medical Genetics, Vol. 60, No. 3, 01.03.2017, p. 149-153.

Research output: Contribution to journalArticle

Ait-Idir, D, Djerdjouri, B, Bouldjennet, F, Taha, R, El-Shanti, H, Sari-Hamidou, R, Khellaf, G, Benmansour, M, Benabadji, M & Haddoum, F 2017, 'The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever', European Journal of Medical Genetics, vol. 60, no. 3, pp. 149-153. https://doi.org/10.1016/j.ejmg.2016.12.003
Ait-Idir, Djouher ; Djerdjouri, Bahia ; Bouldjennet, Faiza ; Taha, Rowaida ; El-Shanti, Hatem ; Sari-Hamidou, Rawda ; Khellaf, Ghalia ; Benmansour, Mustapha ; Benabadji, Mohamed ; Haddoum, Farid. / The M694I/M694I genotype : A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever. In: European Journal of Medical Genetics. 2017 ; Vol. 60, No. 3. pp. 149-153.
@article{d2a7f0f924f84b619af3c913e9072855,
title = "The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever",
abstract = "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.",
keywords = "Algeria, Familial Mediterranean fever, MEFV gene, p.M694I, Renal AA-amyloidosis",
author = "Djouher Ait-Idir and Bahia Djerdjouri and Faiza Bouldjennet and Rowaida Taha and Hatem El-Shanti and Rawda Sari-Hamidou and Ghalia Khellaf and Mustapha Benmansour and Mohamed Benabadji and Farid Haddoum",
year = "2017",
month = "3",
day = "1",
doi = "10.1016/j.ejmg.2016.12.003",
language = "English",
volume = "60",
pages = "149--153",
journal = "European Journal of Medical Genetics",
issn = "1769-7212",
publisher = "Elsevier Masson SAS",
number = "3",

}

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

AU - El-Shanti, Hatem

AU - Sari-Hamidou, Rawda

AU - Khellaf, Ghalia

AU - Benmansour, Mustapha

AU - Benabadji, Mohamed

AU - Haddoum, Farid

PY - 2017/3/1

Y1 - 2017/3/1

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.

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.

KW - Algeria

KW - Familial Mediterranean fever

KW - MEFV gene

KW - p.M694I

KW - Renal AA-amyloidosis

UR - http://www.scopus.com/inward/record.url?scp=85012283726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012283726&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2016.12.003

DO - 10.1016/j.ejmg.2016.12.003

M3 - Article

VL - 60

SP - 149

EP - 153

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 3

ER -