Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype

Tzipora C. Falik-Zaccai, Elena Shachak, Michal Yalon, Zvi Lis, Zvi Borochowitz, James N. Macpherson, David L. Nelson, Evan E. Eichler

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64 Scopus citations

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.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalAmerican Journal of Human Genetics
Volume60
Issue number1
StatePublished - Jan 1997
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesP01GM052982
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR01HD029256

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