title: Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype.
abstract: 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.
authors.affiliation: Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa.
authors.forename: T C
authors.initials: TC
authors.lastname: Falik-Zaccai
authors.forename: E
authors.initials: E
authors.lastname: Shachak
authors.forename: M
authors.initials: M
authors.lastname: Yalon
authors.forename: Z
authors.initials: Z
authors.lastname: Lis
authors.forename: Z
authors.initials: Z
authors.lastname: Borochowitz
authors.forename: J N
authors.initials: JN
authors.lastname: Macpherson
authors.forename: D L
authors.initials: DL
authors.lastname: Nelson
authors.forename: E E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D018912:Arabs / Q000235:genetics; D005260:Female; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D015995:Prevalence; D018911:Trinucleotide Repeats; D014416:Tunisia