Abstract

The fragile X mental retardation allele was investigated in Ibadan, south west Nigeria. Blood specimens from a population of 659 mentally retarded individuals (MRs) were screened for the fragile X mutation using cytogenetic and molecular methods. It was observed that 235 (35.7%) individuals had chromosomal aetiologies to their mental impairment. The Down syndrome was highest occurring in 146 (21.2%) individuals, followed by the fragile X karyotype with 45 (6.83%) individuals expressing the 46, Xq27.3 fragility. Of the fragile X individuals, there were 13 (2.0%) fragile X females, 2 of which were 45, XO/46, XX and 45, XO/46, XX/47, XXX mosaics, respectively. Molecular methods confirmed the cytogenetic findings, where affected individuals expressed the trinucleotide repeat amplification in the order of > 2 00 CGG repeats in the fragile X allele region. Triplet repeat bands ranged between 200 and 2000 CGGs. Eight pedigrees comprising 70 normal relatives of 8 fragile X mentally retarded propositi were permissible to investigations for the determination of interfamilial transmission of the fragile X alleles. Blood samples were equally obtained from them and analysed using cytogenetic and molecular methods likewise. Two normal sisters of a male propositus exhibited the 45, XO/47, XXX and 46, Xr(X)/45, XO mosaicisms, respectively. Molecular analysis revealed 26 (33.3%) female permutation carriers and 11 (14.1%) normal transmitting males. Eighteen (23.1%) males had normal alleles, thus are non-transmitting males, and 15 (19.2%) females were normal. The proportions observed in this survey have implications for the general population and should prove significantly useful for clinicians and genetic counsellors.

Key words: Fragile X syndrome, mental retardation, karyotype, cytogenetic, molecular analysis.