Monosomy of the entire short arm of chromosome 18 as a result of an 18;acrocentric whole arm translocation has been reported in over 20 patients, 3 of which were familial. The centromeric origin in de novo cases has not been characterized. We report molecular cytogenetic studies of two prenatally-detected de novo cases. Amniocenteses were performed because of sonographic findings of fetal holoprosencephaly. Cytogenetic studies and dual color fluorescence in situ hybridization using Oncor alpha-satellite probes for D18Z1 and D13Z1/D21Z1 showed monosomy 18p with presence of a dicentric 18;21 chromosome in both cases [45,XY,dic(18;21)(p11.1;p11.1)]. In one case, a second cell line was found, which contained 46 chromosomes with a del(18)(p11.1) and an apparently telocentric 21 not present in either parent [46,XY,del(18)(p11.1),del(21)(p11.1)]. The del(18)(p11.1) contained only the 18 alphoid sequence and the telocentric 21 contained only the 21 alphoid sequence. No centromeric break was detected. We propose that the second cell line arose from dissociation of the dic(18;21) with no centromeric DNA break. In addition to our case, there have been three previous reports of dissociation of dicentric 18;acrocentric chromosomes indicating that the translocation site can be unstable and dissociate.

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.