TY - JOUR
T1 - Familial Mediterranean fever in Armenians
T2 - Autosomal recessive inheritance with high gene frequency
AU - Rogers, D. B.
AU - Shohat, M.
AU - Petersen, G. M.
AU - Bickal, J.
AU - Congleton, J.
AU - Schwabe, A. D.
AU - Rotter, J. I.
PY - 1989
Y1 - 1989
N2 - 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. The parent-to-offspring transmission of FMF reported in Armenians can be explained by its high gene frequency in this ethnic group. We conclude that, despite the clinical differences, FMF is an autosomal recessive disease in all ethnic groups studied to date.
AB - 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. The parent-to-offspring transmission of FMF reported in Armenians can be explained by its high gene frequency in this ethnic group. We conclude that, despite the clinical differences, FMF is an autosomal recessive disease in all ethnic groups studied to date.
UR - http://www.scopus.com/inward/record.url?scp=0024446455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024446455&partnerID=8YFLogxK
U2 - 10.1002/ajmg.1320340206
DO - 10.1002/ajmg.1320340206
M3 - Article
C2 - 2816993
AN - SCOPUS:0024446455
SN - 0148-7299
VL - 34
SP - 168
EP - 172
JO - American journal of medical genetics
JF - American journal of medical genetics
IS - 2
ER -