Читать книгу Protocols for High-Risk Pregnancies - Группа авторов - Страница 42

The phenotype of trisomy 21 occurs when there is a triplication of dosage‐sensitive genes on chromosome 21; these genes comprise the Down syndrome critical region. Nondisjunction of the chromosome 21 pair during meiosis of the germ cells accounts for 95% of cases of trisomy 21. In the vast majority of cases, the extra chromosome is maternal in origin, and there is a strong correlation between maternal age and the chances of fetal trisomy 21. In less than 5% of cases, the additional chromosome 21 material is a result of an unbalanced translocation, usually affecting chromosomes 14 and 21, but occasionally also involving chromosomes 15 or 22. About 50% of such cases occur as de novo translocations and 50% are inherited from a parent who carries a balanced translocation. Rarer cases of trisomy 21 are mosaic, in which some cell lines carry three copies of chromosome 21, while others are diploid and normal. Trisomies 13 and 18 also occur due to meiotic nondisjunction in approximately 85% of cases, while 10% of cases are mosaic and 5% are due to a translocation.

Copy number variants (CNV) occur when the number of copies of a particular gene or genomic region varies from one individual to the next; these variants can be duplications or deletions. Large CNVs may be detectable by karyotype, but most require chromosomal microarray to be diagnosed. Although small when compared to trisomy of an entire chromosome, CNVs can be associated with significant medical and intellectual disabilities. Unlike the common trisomies, the rate of significant CNVs does not increase with maternal age and is estimated at about 0.5–1% of pregnancies in the mid‐trimester. Therefore, these are more common than Down syndrome and the common aneuploidies in women under age 35.