Abstract
We recently observed an increased frequency of binucleated micronucleated lymphocytes in women who had a Down syndrome (DS) child before 35 years of age and the fluorescence in situ hybridization analysis revealed that micronuclei were mainly originating from chromosomal malsegregation events, including chromosome 21 malsegregation. That study indicated that women who have a DS child at a young age might have a genetic predisposition to chromosome malsegregation in both somatic and germ line cells. Further studies from our group confirmed increased chromosome damage in blood cells of women who had a DS child at a young age and pointed to a possible role for polymorphisms in folate-metabolizing genes in affecting both chromosome damage and DS risk. In the present article, we review the most recent findings on mechanisms and risk factors for chromosome 21 nondisjunction that lead to DS. Multiple risk factors are likely involved in chromosome nondisjunction; they act at different times in the meiotic process and can be of genetic or environmental (epigenetic) origin. We also discuss the increased risk of developing Alzheimer's disease (AD) later in life that was observed in women who had a DS child at a young age. Studies performed in the last years that have shown that the brain is, in fact, a complex genetic mosaic of aneuploid and euploid cells support the unified hypothesis trying to relate DS, trisomy 21, and AD.
Highlights
Down syndrome (DS) or trisomy 21 (MIM 190685) is a genetic disease resulting from the presence and the expression of three copies of genes located on chromosome 21
Several studies were performed in the last years that were aimed at clarifying the possible role of impaired folate metabolism to DS risk; the question is still debated and none of the studied polymorphisms of metabolic genes can be considered undoubtedly as an independent DS risk factor, whereas there is increasing evidence that combinations of two or more of them might affect the risk for a DS pregnancy[22,23,24,25,26,27]
We performed a study aimed at evaluating cytogenetic characteristics, through the micronucleus test, of peripheral blood lymphocytes of a group of women who had a DS child at a young age, in comparison with a control group of mothers who had a healthy child
Summary
Received May 6, 2009; Revised September 9, 2009; Accepted September 21, 2009; Published October 2, 2009. We recently observed an increased frequency of binucleated micronucleated lymphocytes in women who had a Down syndrome (DS) child before 35 years of age and the fluorescence in situ hybridization analysis revealed that micronuclei were mainly originating from chromosomal malsegregation events, including chromosome 21 malsegregation. That study indicated that women who have a DS child at a young age might have a genetic predisposition to chromosome malsegregation in both somatic and germ line cells. Further studies from our group confirmed increased chromosome damage in blood cells of women who had a DS child at a young age and pointed to a possible role for polymorphisms in folate-metabolizing genes in affecting both chromosome damage and DS risk. Multiple risk factors are likely involved in chromosome nondisjunction; they act at different times in the meiotic process and can be of genetic or environmental (epigenetic) origin.
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