Multiple Forms of Atypical Rearrangements Generating Supernumerary Derivative Chromosome 15

Overview

Journal BMC Genet

Publisher Biomed Central

Specialties Biotechnology
Molecular Biology

Date 2008 Jan 8

PMID 18177502

Citations 20

Authors

Nicholas J Wang

Alexander S Parokonny

Karen N Thatcher

Jennette Driscoll

Barbara M Malone

Naghmeh Dorrani

Marian Sigman

Janine M LaSalle

N Carolyn Schanen

Affiliations

Soon will be listed here.

Abstract

Background: Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15)] that has been called inverted duplication 15 or isodicentric 15 [idic(15)], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR) that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15) chromosomes arise through BP3:BP3 or BP4:BP5 recombination events.

Results: Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15), we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15) and the normal homologues.

Conclusion: Involvement of atypical BP in the generation of idic(15) chromosomes can lead to considerable structural heterogeneity.

Citing Articles

Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain.

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Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain.

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Optical genome mapping enables constitutional chromosomal aberration detection.

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Possible Phenotypic Consequences of Structural Differences in Idic(15) in a Small Cohort of Patients.

Czako M, Till A, Szabo A, Ripszam R, Melegh B, Hadzsiev K Int J Mol Sci. 2019; 20(19).

PMID: 31590400 PMC: 6801911. DOI: 10.3390/ijms20194935.

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