PREDISPOSITION TO THE FRAGILE-X-SYNDROME IN JEWS OF TUNISIAN DESCENT IS DUE TO THE ABSENCE OF AGG INTERRUPTIONS ON A RARE MEDITERRANEAN HAPLOTYPE

We have studied the ethnic distribution of the fragile X syndrome in I srael and have found that 36/136 (26.5%) of apparently unrelated pedig rees were of Tunisian Jewish descent, The Tunisian Jews, however, cons titute only 2%-3% of the general Israeli population, identifying the f irst ethnic group significantly (P < .001) predisposed to the developm ent of this disease, Associated with this increase in disease prevalen ce, we have found an unusually high incidence of FMR1 CGG repeats devo id of AGG interruptions among the normal Tunisian Jewish population (3 0/150, 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 amon g non-Tunisian Jewish controls in Israel (1/136), Haplotype analysis h as indicated that these large uninterrupted CGG repeat alleles are pre sent on a previously unreported (DXS548-FRAXAC1-FRAXAC2) haplotype tha t accounts for all observed cases of disease among Tunisian Jewish X c hromosomes, The high prevalence of disease among Tunisian Jews, we sug gest, is due to a founder effect of this rare haplotype, which is comp letely devoid of AGG interruptions in the Jewish population of Tunisia .