The main aim of the present study was detection of the frequency of MTHFR gene mutation in Egyptians as a risk factor for nondisjunction. Mothers were subjected to complete nutritional history, estimation of homocysteine level in blood and study of MTHFR mutation at site 677. The results showed absence of MTHFR gene mutation in D.S. mothers and control mothers. Folate intake was significantly low in mothers with D.S. children. This indicates that sufficient folate (400 µg/d) is important preventive strategy, for nondisjunction. Blood homocysteine was normal in both D.S. mothers, which indicate that homocysteine is affected by other factors than folate intake.