Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism

Abstract

Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.

Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes

“…However, trisomy 8 may also be constitutional, occurring as a mosaicism (CT8M) in approximately 0.1% of all recognized pregnancies [32]. Typically, CT8M is the consequence of a postzygotic nondisjunction, and as expected for a gain arising through this mechanism, there is no preferential parental origin of the extra chromosome [33,34]. CT8M is associated with mild to moderate mental retardation, facial dysmorphic features, bone and joint abnormalities, and cardiovascular and urogenital malformations; however, some present with an apparently normal phenotype, including normal intelligence [35].…”

Maternal uniparental isodisomy 20 in a foetus with trisomy 20 mosaicism: clinical, cytogenetic and molecular analysis

“…The validity of this PCR method for dosage analysis has previously been demonstrated by densitometry, 22 and in the case of mosaicism the extra chromosome can be detected by dosage analysis when the trisomic cell line is present in at least 20% of the cells analysed. 23 Markers heterozygous in the parent contributing the extra chromosome were identified and scored in the proband as reduced or non-reduced to homozygosity. 24 …”

Constitutional Trisomy 8 Mosaicism with Persistent Macrocytosis

“…Although CT8M is compatible with life, it has extremely variable phenotypes ranging from normal features to severe malformations [Alkuraya and Harris, 2005;Agrawal and Agrawal, 2011]. Complete trisomy 8 is thought to result from meiotic nondisjunction, whereas CT8M is thought to result from a post-zygotic event [Karadima et al, 1998;Alkuraya and Harris, 2005].…”