Centromeric dna break in a 10;16 reciprocal translocation associated with trisomy 16 confined placental mosaicism and maternal uniparental disomy for chromosome 16

Abstract

Stable centromeric breakage in non-acrocentric chromosomes and balanced reciprocal translocation mosaicism are both rare events. We studied a family in which the mother had mosaicism for a balanced reciprocal translocation between chromosomes 10 and 16 which was associated with a break in chromosome 16 centromere alpha-satellite DNA ¿146,XX,t(10;16)(q11.2;q11.1) [29]/46,XX[25]¿. The derivative chromosome 16 contained only a very small amount of 16 alpha-satellite DNA while the derivative 10 contained all of the 10 alpha-satellite DNA as well as a large amount of the 16 alpha-satellite DNA. The same translocation was present in all cells in her son who was found prenatally to have trisomy 16 mosaicism ¿46,XY,t(10;16) (q11.2;q11.1)mat[22]/47,idem,+16[4]¿. Trisomy 16 cells were subsequently determined to be confined to the placenta. DNA polymorphism analyses in the family demonstrated maternal uniparental disomy for chromosome 16 in the diploid child. The child, at age 7 months, had minor facial anomalies similar to a previously reported case of maternal uniparental disomy for chromosome 16. In addition to illustrating several rare events, this family further demonstrated that substantial deletion of the centromeric alpha-satellite DNA does not impair centromere function and both mitotic and meiotic stability are retained in such cases.

Mosaic trisomy 16 ascertained through amniocentesis: Evaluation of 11 new cases

“…Two of these (including one case that also showed true mosaicism) had abnormal phenotypes, whereas one was reported as normal at 21 weeks of gestation. Previously reported cases of UPD for chromosome 16 [Lindor et al, 1993;Kalousek et al, 1993;Sutcliffe et al, 1993;Vaughan et al, 1994;Whiteford et al, 1995;Schneider et al, 1996;Hsu et al, 1997;Robinson et al, 1997;Woo et al, 1997;Wang et al, 1997] as well as the three cases reported here indicate that intrauterine growth retardation is a frequent consequence but that a diversity of congenital anomalies may occur as well. An extensive review of prenatally detected trisomy 16 [Wolstenholme, 1995] indicates that maternal UPD 16 has been associated with pregnancy loss in the second or early third trimester as well as early delivery with severe growth retardation.…”

“…Including this series, 33 cases of mosaic trisomy 16 detected through amniocentesis have been reported to date. Of 21 continuing pregnancies, 16 pregnancies (77%) had abnormal outcomes, including neonatal death [Watson et al, 1988;Devi et al, 1993], or liveborns with some combination of IUGR, CHD, and minor anomalies [Lindor et al, 1993;Pletcher et al, 1994;Paulyson et al, 1996;Devi et al, 1997;Hsu et al, 1997;Smith et al, 1997;Wang et al, 1997]. The remaining five pregnancies produced infants with an apparently normal phenotype at birth .…”

“…All three continuing pregnancies, in which cells with trisomy 16 were identified in the placenta, resulted in early delivery (28 to 34 weeks), perhaps a result of the malfunction of placenta caused by high levels of trisomic cells. Of the 20 reported cases of trisomy 16 mosaicism detected at amniocentesis, in which the placenta and/or other extra embryonic tissues were available for study [Watson et al, 1988;Huff et al, 1991;Lindor et al, 1993;Pletcher et al, 1994;Tantravahi et al, 1996;Paulyson et al, 1996;Hsu et al, 1997;Devi et al, 1997;Smith et al, 1997;Wang et al, 1997], 19 (95%) had cells with trisomy 16. Among the 13 continuing pregnancies, 11 (85%) resulted in premature delivery and/or IUGR.…”

“…Hence, the more recent reports of cases of mosaic trisomy 16 detected by amniocentesis are somewhat surprising. These reports indicate that trisomy 16 mosaicism can be associated with neonatal death [Watson et al, 1988;Devi et al, 1993], live births with multiple congenital anomalies [Pletcher et al, 1994;Paulyson et al, 1996;Devi et al, 1997;Smith et al, 1997;Wang et al, 1997], live births with relatively mild but still abnormal phenotypes [Lindor et al, 1993], or live births with normal phenotype . Six electively terminated fetuses with mosaic trisomy 16 detected by amniocentesis were abnormal showing IUGR, congenital cardiac anomalies (atrial septal defect, ventricular septal defect, and tetralogy of Fallot), severe pulmonary hypoplasia, horseshoe or ectopic kidney, thymic and adrenal atrophy, single umbilical artery, and minor facial anomalies [Huff et al, 1991;Davies et al, 1995;Tantravahi et al, 1996;Hsu et al, 1997].…”

Review and meta‐analysis of systematic searches for uniparental disomy (UPD) other than UPD 15

“…However, so far, in three studies comprising 52 cases, no case of UPD was found [James et al, 1994; May et al, 1994; Miny et al, 1994]. In the literature, only five cases were reported; in three of them chromosome 15 was participating and UPD 15 was found [Smeets et al, 1992; Smith et al, 1994; Park et al, 1998], while chromosome 16 was in the remaining two [Dupont et al, 1998; Wang et al, 1998]. Four of these cases were found by a phenotype specific for one of the chromosomes involved [Smeets et al, 1992; Smith et al, 1994; Dupont et al, 1998; Park et al, 1998].…”