Evidence for the repeated primary non-disjunction of chromosome 21 as a result of premature centromere division (PCD)

Fitzgerald, P. H.; Archer, Susan A.; Morris, Christine M.

doi:10.1007/bf00278818

Cited by 52 publications

(25 citation statements)

References 18 publications

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“…Two independent de novo events are possible although the likelihood at this young age is quite low. Another possible explanation is gonadal mosaicism [Beratis et al, 1972;Fitzgerald et al, 1986], which could have potentially been proven by molecular marker analysis.…”

Section: Discussionmentioning

confidence: 99%

Survival with trisomy 18—data from Switzerland

Niedrist

Riegel

Achermann³

et al. 2006

American J of Med Genetics Pt A

106

105

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We collected records of 352 cases of trisomy 18 karyotyped between 1964 and May 2003 from the two major cytogenetic laboratories in Northeastern Switzerland. For more detailed information about the cases we contacted the referring physicians and/or the families of the patients. In this way we collected data about survival and malformations of 161 live births, 136 induced abortions and 29 stillborns or spontaneous abortions. In 26 cases of trisomy 18, only incomplete records were available. We observed that each year more cases of trisomy 18 were cytogenetically diagnosed in the two laboratories. Before 1984 almost no prenatal diagnoses were made; however, after this date the number of prenatal diagnoses increased and in the last 10 years, accounted for 75% of all cases. A decrease in the number of postnatally diagnosed cases was also observed over the same period of time. One third of the live-born children with trisomy 18 died during the first day of life. After 1 week, 1 month and 1 year of life the survival rates were 40, 22 and 6%, respectively. The median survival was 4 days, and only 1% of the children survived until their 10th birthday. Females were more likely to survive long term. In 63 cases autopsy reports were available for review. In 97% of these cases three or more malformations were found: 67% had VSD, 32% had horseshoe kidneys, 21% had esophageal atresia, 14% had omphalocele, 14% had facial clefts, and 11% had diaphragmatic hernias. In more than 50% genital hypoplasia was also described. We further analyzed survival of live-borns in relation to the length of gestation and to VSD and esophageal atresia. ß 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Survival with trisomy 18—data from Switzerland

Niedrist

Riegel

Achermann³

et al. 2006

American J of Med Genetics Pt A

106

105

View full text Add to dashboard Cite

show abstract

“…Individuals with PCD were usually clinically normal, but there was sometimes an association with multiple spontaneous abortions or sterility (Rudd et al 1983;Gabarron et al 1986). Fitzgerald et al (1986) reported a clinically normal woman with three conceptuses with trisomy 21 who had PCD in some chromosomes. It was proposed that PCD may result in aneuploid cell lines because prematurely separated centromeres apparently cannot attach to the spindle fibers and this produces non-disjunction.…”

Section: Discussionmentioning

confidence: 99%

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature

et al. 1999

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We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including DandyWalker malformation), and possible cancer predisposition.

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“…As a kind of chromosomal alteration, phenomenon of premature centromere division (PCD) was observed in sporadic Alzheimer disease (SAD) [6,8,12,19]. PCD represents a loss of control over sequential separation and segregation of chromosome centromeres, characterized by distinctive separation of chromosomes earlier than usual [20,21]. This phenomenon shows that deregulation of the time of centromere separation can be considered as a manifestation of CIN leading to aneuploidy [19,22,23,24].…”

Section: Introductionmentioning

confidence: 99%

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

et al. 2013

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While Alzheimer disease (AD) is considered a neurodegenerative disorder, the importance of chromosome instability in non-neuronal cells is equally important, not only for shedding light on the etiology of the disease, but also for possible diagnostic purposes and monitoring the progress of the disease. Here, we evaluated the frequency of DNA damage and expression of premature centromere division (PCD) in peripheral blood lymphocytes of sporadic AD patients, age-matched and young controls. The results show that in male patients with AD, the frequencies of PCD and DNA damage were significantly greater (88%, p < 0.01 and 38%, p < 0.05, respectively) than in age-matched control group. AD females had significantly increased frequency of PCD (134%, p < 0.01) as well as a higher frequency of DNA damage (37%, p < 0.05). Ageing per se, both in males and females, shows significant increase of percentages of PCD (2.3 times, p < 0.01 and 2.8 times, p < 0.01, respectively) and DNA damage (63%, p < 0.01 and 50%, p < 0.01, respectively) comparing with young controls. In addition, a strong (R² = 0.873, n = 6) and significant (p < 0.01) correlation between the frequencies of PCD and DNA damage was found in all examined groups. We may conclude that the increases in both parameters evaluated in this study are not only associated with normal ageing processes, but are markedly and significantly intensified in AD pathogenesis. Thus, our data support the view that AD is a generalized systemic disease, at least as for the increased DNA damage and PCD incidence in peripheral blood cells.

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Evidence for the repeated primary non-disjunction of chromosome 21 as a result of premature centromere division (PCD)

Cited by 52 publications

References 18 publications

Survival with trisomy 18—data from Switzerland

Survival with trisomy 18—data from Switzerland

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

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