PCR Based Detection of Parental Origin of Extra Chromosome 21 in Children with Down Syndrome in Pakistan

Down syndrome, the most frequent form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterized by well-defined and distinctive phenotypic features. It is caused by triplicate state (trisomy) of all or a critical portion of chromosome 21. The risk of having a child with trisomy 21 increases with maternal age. Out of the total thirty patients 53.3% were males and 46.6% were females. Down syndrome is slightly common in male children than in females. The parental origin of the extra chromosome has been studied in thirty families each with a clinically suspected trisomy 21 proband. Molecular analysis was carried out by PCR based method, using polymorphic microsatellite markers D21S11 and D21S2055 situated on the long arm of the chromosome 21 at 21q21 and 21q22 respectively. The amplified products were subjected to polyacrylamide gel electrophoresis and alleles were scored by staining with ethidium bromide. Trisomy 21 was detected by the presence of three distinct alleles and transmission of alleles from parents to the offspring was determined in all but five families. Parental origin was found to be maternal in twenty three families and paternal in two families. The mean maternal and paternal ages of subjects were 25.1 ± 6.9 and 30.9 ± 6.9 years respectively. The results showed the use of molecular diagnosis for the allelic transmission from the parents to offspring and also emphasize the fact that the trisomy 21 was due to meiotic errors in maternal chromosomes.