Fragile X syndrome (FXS) is identified as the leading monogenic cause of autism and congenital mental retardation. It is estimated that the frequency of FXS is 1/7000 males and 1/11,000 women (Hunter et al., 2014). In Australia, since one child is born with Fragile X every week, around 1 in 3600 boys and in 4000 – 6000 girls suffers this syndrome with the higher severity in boys.
Position of the causative gene for FXS named fragile X mental retardation gene 1 (FMR1) was found at the diagnostic fragile site – cytogenetic position Xq27.3 after being cloned in 1991 (Verkerk et al., 1991). The most encountered mutation in FXS diagnosis is the repetition of a trinucleotide complex CGG in the 5’ untranslated region (UTR) of FMR1. The usual length …show more content…
Surprisingly, the inheritance pattern of FXS can also affect females (Sherman et al., 2005). Because of the presence of two X chromosomes, there is a 50% chance that the mutated X chromosome might pass from a mother with a premutation or full mutation to her children in each pregnancy. If the alteration is passed on, it may remain a premutation or expand to a full mutation (premutated mothers) or remain a full mutation (fully mutated mothers). Unlike the usual observation in typical X-linked diseases that all males carrying other abnormal X-linked are affected, the dominant number of male obligate carriers with over 60 CGG repeats in the pedigrees show no symptoms. If fathers have a premutation, all their daughters will receive the premutated genes. Moreover, the rate of FXS development is higher for the grandchildren of these healthy male carriers compared to the siblings of the carriers. The molecular basis behind this unusual genetic anticipation - Sherman paradox remains a mystery.
In conclusion, fragile X syndrome caused by an expansion of CGG repeats raging from 60 to over 200 at the 5’ UTR of FMR1 on X chromosome leads to the impairment of FMR1’s product FMRP, resulting in autistic-like behaviors, growth abnormalities and difficulties in learning and concentrating since FMRP is necessary for the regulation of dendritic mRNAs’ translation. Because the inheritance pattern of FXS does not follow typical X-linked diseases, it influenced not only males (mainly shown as macroorchidism prior to puberty) but also female
Position of the causative gene for FXS named fragile X mental retardation gene 1 (FMR1) was found at the diagnostic fragile site – cytogenetic position Xq27.3 after being cloned in 1991 (Verkerk et al., 1991). The most encountered mutation in FXS diagnosis is the repetition of a trinucleotide complex CGG in the 5’ untranslated region (UTR) of FMR1. The usual length …show more content…
Surprisingly, the inheritance pattern of FXS can also affect females (Sherman et al., 2005). Because of the presence of two X chromosomes, there is a 50% chance that the mutated X chromosome might pass from a mother with a premutation or full mutation to her children in each pregnancy. If the alteration is passed on, it may remain a premutation or expand to a full mutation (premutated mothers) or remain a full mutation (fully mutated mothers). Unlike the usual observation in typical X-linked diseases that all males carrying other abnormal X-linked are affected, the dominant number of male obligate carriers with over 60 CGG repeats in the pedigrees show no symptoms. If fathers have a premutation, all their daughters will receive the premutated genes. Moreover, the rate of FXS development is higher for the grandchildren of these healthy male carriers compared to the siblings of the carriers. The molecular basis behind this unusual genetic anticipation - Sherman paradox remains a mystery.
In conclusion, fragile X syndrome caused by an expansion of CGG repeats raging from 60 to over 200 at the 5’ UTR of FMR1 on X chromosome leads to the impairment of FMR1’s product FMRP, resulting in autistic-like behaviors, growth abnormalities and difficulties in learning and concentrating since FMRP is necessary for the regulation of dendritic mRNAs’ translation. Because the inheritance pattern of FXS does not follow typical X-linked diseases, it influenced not only males (mainly shown as macroorchidism prior to puberty) but also female