TY - JOUR
T1 - Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype
AU - Falik-Zaccai, Tzipora C.
AU - Shachak, Elena
AU - Yalon, Michal
AU - Lis, Zvi
AU - Borochowitz, Zvi
AU - Macpherson, James N.
AU - Nelson, David L.
AU - Eichler, Evan E.
PY - 1997/1
Y1 - 1997/1
N2 - We have studied the ethnic distribution of the fragile X syndrome in Israel and have found that 36/136 (26.5%) of apparently unrelated pedigrees were of Tunisian Jewish descent. The Tunisian Jews, however, constitute only 2%-3% of the general Israeli population, identifying the first ethnic group significantly (P < .001) predisposed to the development of this disease. Associated with this increase in disease prevalence, we have found an unusually high incidence of FMR1 CGG repeats devoid of AGG interruptions among the normal Tunisian Jewish population (30/150, or 20.0%). Furthermore, the proportion of these alleles beyond the FMR1 CGG repeat instability threshold (>35 repeats) (8/150, or 5.3%) was significantly greater (P < .04) than that proportion found among non-Tunisian Jewish controls in Israel (1/136). Haplotype analysis has indicated that these large uninterrupted CGG repeat alleles are present on a previously unreported (DXS548-FRAXAC1- FRAXAC2) haplotype that accounts for all observed cases of disease among Tunisian Jewish X chromosomes. The high prevalence of disease among Tunisian Jews, we suggest, is due to a founder effect of this rare haplotype, which is completely devoid of AGG interruptions in the Jewish population of Tunisia.
AB - We have studied the ethnic distribution of the fragile X syndrome in Israel and have found that 36/136 (26.5%) of apparently unrelated pedigrees were of Tunisian Jewish descent. The Tunisian Jews, however, constitute only 2%-3% of the general Israeli population, identifying the first ethnic group significantly (P < .001) predisposed to the development of this disease. Associated with this increase in disease prevalence, we have found an unusually high incidence of FMR1 CGG repeats devoid of AGG interruptions among the normal Tunisian Jewish population (30/150, or 20.0%). Furthermore, the proportion of these alleles beyond the FMR1 CGG repeat instability threshold (>35 repeats) (8/150, or 5.3%) was significantly greater (P < .04) than that proportion found among non-Tunisian Jewish controls in Israel (1/136). Haplotype analysis has indicated that these large uninterrupted CGG repeat alleles are present on a previously unreported (DXS548-FRAXAC1- FRAXAC2) haplotype that accounts for all observed cases of disease among Tunisian Jewish X chromosomes. The high prevalence of disease among Tunisian Jews, we suggest, is due to a founder effect of this rare haplotype, which is completely devoid of AGG interruptions in the Jewish population of Tunisia.
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C2 - 8981953
AN - SCOPUS:0031038239
SN - 0002-9297
VL - 60
SP - 103
EP - 112
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -