centric inversion (one involving the centromere) or paracentric inversion (not involving the centromere). Individuals with pericen tric inversions are at increased risk for producing offspring with a duplication/deletion. Those with paracentric inversions are at increased risk for early pregnancy loss.
A mosaic individual has two or more cytogenetically distinct cell lines that are derived from a single zygote. Phenotypic expression of mosaicism depends on several factors, including whether the cytogenetically abnormal cells involve the fetus, part of the fetus, just the placenta, or some combination. Of amnionic luid cultures, mosaicism is found in approximately 0.3 percent but may not reflect the fetal chromosomal complement (Carey, 2014). When the abnormal cells are present in only a single lask of amnionic luid, the inding is likely pseudomosaicism, caused by cell-culture artifact (Bui, 1984; Hsu, 1984). When abnormal cells involve multiple cultures, however, true mosaicism is more likely, and further testing may be warranted. A second cell line is veriied in 60 to 70 percent of these fetuses (Hsu, 1984; Worton, 1984).
With chorionic villus sampling, studies demonstrate that up to 2 percent of placentas are mosaic, with the mosaicism conined to the in most of these cases (Bafero, 2012; Henderson, 1996). Amniocentesis should be ofered. In a series of more than 1000 pregnancies with mosaicism found from chorionic villus sampling, subsequent amniocentesis identiied true fetal mosaicism in 13 percent. Uniparental disomy, discussed later (p. 268), was found in 2 percent, and the remainder resulted from confined placental mosaicism (Malvestiti, 2015).
If mosaicism is detected for a chromosome known to contain imprinted genes-such as chromosomes 6, 7, 11, 14, or 15testing for uniparental disomy should be considered, as there may be fetal consequences (Grati, 2014a).
lthough outcomes with conined placental mosaicism are generally good, fetal-growth restriction is more common, and the stillbirth risk is also higher (Reddy, 2009). Fetal-growth restriction may stem from impaired functioning of the aneuploid placental cells (Bafero, 2012). Placental mosaicism for trisomy 16 confers a particularly poor prognosis.
Mosaicism confined to the gonads likely arises from a mitotic error in cells destined to become the gonad, resulting in a population of abnormal germ cells. Because spermatogonia and oogonia divide throughout fetal life, and spermatogonia continue to divide throughout adulthood, gonadal mosaicism may also follow a meiotic error in previously normal germ cells. Gonadal mosaicism can account for de novo diseases in the ofspring of normal parents. Autosomal dominant examples are achondroplasia and osteogenesis imperfecta, and X-linked ones include Duchenne muscular dystrophy. Gonadal mosaicism also explains the 6-percent recurrence risk after the birth of a child with a disease caused by a "new" mutation.