Interstitial Deletion of Proximal 8q Including Part of the Centromere from Unbalanced Segregation of a Paternal Deletion/marker Karyotype with Neocentromere Formation at 8p22

Overview

Journal Cytogenet Genome Res

Specialty Genetics

Date 2011 Jan 8

PMID 21212645

Citations 3

Authors

R D Burnside

J Ibrahim

C Flora

S Schwartz

J H Tepperberg

P R Papenhausen

P E Warburton

Affiliations

Soon will be listed here.

Abstract

Background/aims: The 'McClintock mechanism' of chromosome breakage and centromere misdivision, in which a deleted chromosome with its concomitant excised marker or ring chromosome is formed, has been described in approximately one dozen reports. We report a case of a girl with short stature, developmental delay, and dysmorphic features.

Methods: Analysis was performed on the proband and father using cytogenetic chromosome analysis and the Affymetrix 6.0 SNP microarray. Fluorescence in situ hybridization (FISH) using a chromosome 8 alpha-satellite probe and immunofluorescence with antibodies to CENP-C were used to examine the centromere positions in these chromosomes.

Results: An abnormal chromosome 8 with a cytogenetically visible deletion was further defined by SNP array as a 10.6-Mb deletion from 8q11.1→q12.1. FISH with a chromosome 8 alpha-satellite probe demonstrated that the deletion removed a significant portion of the pericentromeric alpha-satellite repeat sequences and proximal q arm. The deleted chromosome 8 appeared to have a constriction at 8p22, suggesting the formation of a neocentromere, even though alpha-satellite sequences still appeared at the normal location. Chromosome analysis of the phenotypically normal father revealed the same deleted chromosome 8, as well as an apparently balancing mosaic marker chromosome 8. FISH studies revealed that the majority of the chromosome 8 alpha-satellite DNA resided in the marker chromosome. Immunofluorescence studies with antibodies to CENP-C, a kinetochore protein, proved the presence of a neocentromere at 8p22. The excision of the marker from the deleted chromosome 8 likely necessitated the formation of a new kinetochore at the 8p22 neocentromere to stabilize the chromosome during mitosis.

Conclusion: This case clearly illustrates the utilization of classic cytogenetics, FISH, and array technologies to better characterize chromosomal abnormalities and provide information on recurrence risks. It also represents a rare case where a neocentromere can form even in the presence of existing alpha-satellite DNA.

Citing Articles

The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA.

Barra V, Fachinetti D Nat Commun. 2018; 9(1):4340.

PMID: 30337534 PMC: 6194107. DOI: 10.1038/s41467-018-06545-y.

Neocentromeres to the Rescue of Acentric Chromosome Fragments.

Poot M Mol Syndromol. 2017; 8(6):279-281.

PMID: 29230156 PMC: 5701270. DOI: 10.1159/000481332.

Neocentromeres and epigenetically inherited features of centromeres.

Burrack L, Berman J Chromosome Res. 2012; 20(5):607-19.

PMID: 22723125 PMC: 3409321. DOI: 10.1007/s10577-012-9296-x.

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