Implication of screening for FMR1 and FMR2 gene mutation in individuals with nonspecific mental retardation in Taiwan

Fragile X syndrome (FXS) is the most common form of familial mental retardation (MR), attributable to (CGG)n expansion in the FMR1 gene. FRAXE is less frequent, associated with a similar mutation of the FMR2 gene. This study attempted to ascertain the prevalence of both disorders in Taiwan, as well as to develop a method to effectively find carriers. A total of 321 patients with nonspecific MR were screened for the FMR1 and FMR2 mutation. Four of 206 boys and men (1.9%) and 1 in 115 girls and women (0.9%) were identified as having FXS. All four FXS boys or men could be identified by Southern blot analysis, as well as by a simple nonradioactive polymerase chain reaction analysis. None of the 206 boys or men had FMR2 full mutation. This confirmed the low incidence of FRAXE in Chinese. FXS appears to be more prevalent among patients with mild MR, because 4 of the 5 patients with FXS were from the 115 with mild MR (3.48%) and only 1 was from the other 206 with severe MR (0.49%). All five FXS cases were maternally inherited. Other family members were resistant to further searching for carriers. it is worth noting that none of these mothers had a discernible premarital family history of MR. Thus the negative family history could not preclude the possibility that a woman was a carrier. To identify female carriers of childbearing age, beyond the scope of family history, is thus worthy of further exploration. Screening men for carriers using this inexpensive method is probably feasible, even though normal transmitting men have no immediate risk of producing a child with the disease. Female carriers can then be effectively identified from these normal transmitting men and can take all preventive measures.