Aneuploidy and Intellectual Disability
نویسندگان
چکیده
Aneuploidy is the presence of an abnormal number of chromosomes in cells. The gain or loss of a chromosome in germ cells is the most common cause of chromosomal aneuploidy. Trisomy 21, trisomy 18, and trisomy 13 are characterized by congenital anomalies with intellectual disability (ID) or short lives. Recently, mosaic variegated aneuploidy (the presence of a different number of chromosomes in some cells) has been reported to be associated with ID and growth retardation, with or without microcephaly and tumors. In the cell cycle, the alignment of sister chromatids at metaphase plates is essential for the equational separation of chromatids. Misaligned chromosomes at metaphase plates, and/or aberration of the mitotic checkpoint, cause a disproportionate separation of chromatids, resulting in aneuploidy. To evaluate the association between aneuploidy and ID, we analyzed the chromosome numbers of over 200 metaphase plates of lymphoblastoid cells in patients with moderate or severe ID, with or without microcephaly. In this chapter, we summarize the previously reported cases and our own cases of patients with ID associated with aneuploidy or severely misaligned chromosomes at metaphase, and discuss the molecular mechanism underlying ID in cases in which aneuploidy is observed.
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