Genotype/phenotype correlations in Arab patients with familial Mediterranean fever

Hasan A. Majeed, Hatem El-Shanti, Mohammed S. Al-Khateeb, Z. Abu Rabaiha

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Objectives: To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF). Patients and Methods: The study was performed in a 3-year period (February 1998-February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened. Results: Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14 ± 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 ± 3) and M694I/M694I (mean severity score, 6 ± 1) groups was statistically significant (P = .003 and .0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 ± 2) was not statistically significant (P = 0.31). Conclusions: The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalSeminars in Arthritis and Rheumatism
Volume31
Issue number6
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Familial Mediterranean Fever
Genetic Association Studies
Mutation
Genotype
Exons
Jordan
RNA Splice Sites
DNA Restriction Enzymes
Pediatrics

Keywords

  • Familial Mediterranean fever gene mutations
  • Genotype-phenotype correlation
  • Marinostrin
  • Pyrin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Genotype/phenotype correlations in Arab patients with familial Mediterranean fever. / Majeed, Hasan A.; El-Shanti, Hatem; Al-Khateeb, Mohammed S.; Rabaiha, Z. Abu.

In: Seminars in Arthritis and Rheumatism, Vol. 31, No. 6, 2002, p. 371-376.

Research output: Contribution to journalArticle

Majeed, Hasan A. ; El-Shanti, Hatem ; Al-Khateeb, Mohammed S. ; Rabaiha, Z. Abu. / Genotype/phenotype correlations in Arab patients with familial Mediterranean fever. In: Seminars in Arthritis and Rheumatism. 2002 ; Vol. 31, No. 6. pp. 371-376.
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abstract = "Objectives: To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF). Patients and Methods: The study was performed in a 3-year period (February 1998-February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened. Results: Of the 278 patients, 50 (18{\%}) had 2 mutations identified, and 76 (27{\%}) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30{\%}, 16{\%}, and 14{\%}, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78{\%} of mutations. The difference in the mean severity score (14 ± 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 ± 3) and M694I/M694I (mean severity score, 6 ± 1) groups was statistically significant (P = .003 and .0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 ± 2) was not statistically significant (P = 0.31). Conclusions: The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease.",
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N2 - Objectives: To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF). Patients and Methods: The study was performed in a 3-year period (February 1998-February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened. Results: Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14 ± 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 ± 3) and M694I/M694I (mean severity score, 6 ± 1) groups was statistically significant (P = .003 and .0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 ± 2) was not statistically significant (P = 0.31). Conclusions: The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease.

AB - Objectives: To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF). Patients and Methods: The study was performed in a 3-year period (February 1998-February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened. Results: Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14 ± 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 ± 3) and M694I/M694I (mean severity score, 6 ± 1) groups was statistically significant (P = .003 and .0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 ± 2) was not statistically significant (P = 0.31). Conclusions: The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease.

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