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Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency
D B Rogers1, M Shohat, G M Petersen
1Department of Pediatrics, Harbor-UCLA Medical Center, Torrance.
Abstract:
Familial Mediterranean fever (FMF) is a recurrent episodic inflammatory disorder of unknown pathogenesis that occurs with high frequency in non-Ashkenazi Jews and Armenians. However, there are some differences in the clinical manifestations of FMF in these ethnic groups. FMF has been reported to be an autosomal recessive disease in non-Ashkenazi Jews, with a male/female ratio of 1.7, indicating reduced penetrance in females. However, the inheritance is less clear for Armenians. To resolve this problem, we studied prospectively families of 64 Armenian index cases randomly ascertained at the UCLA FMF clinic. Fifty-three families containing 176 sibs in addition to the probands were analyzed by genetic segregation analysis (exclusions included: six single-child families, four families in which one of the parents was also affected, and a family with incomplete information). Upper and lower bounds of the segregation ratio were estimated, and ranged from .10 +/- .03 to .18 +/- .05 when only definitely affected sibs were classified as affected; .17 +/- .04 to .27 +/- .05 when considering "possibly affected" sibs as affected; and .19 +/- .04 to .30 +/- .05 when incomplete penetrance in females was corrected. A value of .25 is the expected segregation ratio for autosomal recessive inheritance, and our data are consistent with this mode of inheritance. We can reject autosomal dominant inheritance, where the expected segregation ratio is .5. Using extended pedigree data, we calculated an FMF gene frequency of 0.073 and a carrier rate of 1/7, which is about four times the frequency in non-Ashkenazi Jews.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Familial Mediterranean fever (FMF) in Armenians follows autosomal recessive inheritance, with a carrier rate of 1/7. This finding clarifies the genetic basis of FMF in this ethnic group.
Area of Science:
- Genetics
- Immunology
Background:
- Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder with unknown causes, prevalent in non-Ashkenazi Jews and Armenians.
- Clinical manifestations and inheritance patterns of FMF can differ between ethnic groups.
- Previous studies suggested autosomal recessive inheritance in non-Ashkenazi Jews, but the pattern in Armenians was unclear.
Observation:
- This study prospectively analyzed 53 Armenian families with 176 siblings from 64 index cases.
- Genetic segregation analysis was performed, excluding certain family types to ensure data integrity.
- Segregation ratios were estimated, considering different classifications of affected individuals and incomplete penetrance in females.
Findings:
- The estimated segregation ratios for FMF in Armenians are consistent with autosomal recessive inheritance (expected ratio of 0.25).
- Autosomal dominant inheritance (expected ratio of 0.5) was rejected based on the data.
- The calculated FMF gene frequency in Armenians is 0.073, with a carrier rate of approximately 1/7.
Implications:
- This research clarifies the genetic transmission of FMF in the Armenian population.
- The findings suggest a higher carrier rate of the FMF gene in Armenians compared to non-Ashkenazi Jews.
- Understanding the genetic basis is crucial for diagnosis, genetic counseling, and potential therapeutic strategies for FMF.