scholarly journals Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects

2011 ◽  
Vol 2 (2) ◽  
pp. 81-87 ◽  
Author(s):  
J. Breckpot ◽  
B. Thienpont ◽  
M. Gewillig ◽  
K. Allegaert ◽  
J.R. Vermeesch ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Congenital Heart Defects ◽  
Copy Number ◽  
Congenital Heart ◽  
Heart Defects ◽  
Monozygotic Twins ◽  
Chromosomal Mosaicism ◽  
Number Variation

Challenges of Interpreting Copy Number Variation in Syndromic and Non-Syndromic Congenital Heart Defects

2011 ◽  
Vol 135 (3-4) ◽  
pp. 251-259 ◽  
Author(s):  
J. Breckpot ◽  
B. Thienpont ◽  
Y. Arens ◽  
L.C. Tranchevent ◽  
J.R. Vermeesch ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Congenital Heart Defects ◽  
Copy Number ◽  
Congenital Heart ◽  
Heart Defects ◽  
Number Variation

scholarly journals Copy number variation as a genetic basis for heterotaxy and heterotaxy-spectrum congenital heart defects

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150406 ◽  
Author(s):  
Jason R. Cowan ◽  
Muhammad Tariq ◽  
Chad Shaw ◽  
Mitchell Rao ◽  
John W. Belmont ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Copy Number ◽  
Congenital Heart ◽  
Heart Defects ◽  
Copy Number Variants ◽  
Loss Of Function ◽  
Pathogenic Cnvs ◽  
Number Variation ◽  
Left Right Asymmetry ◽  
Genomic Disorders

Genomic disorders and rare copy number abnormalities are identified in 15–25% of patients with syndromic conditions, but their prevalence in individuals with isolated birth defects is less clear. A spectrum of congenital heart defects (CHDs) is seen in heterotaxy, a highly heritable and genetically heterogeneous multiple congenital anomaly syndrome resulting from failure to properly establish left–right (L-R) organ asymmetry during early embryonic development. To identify novel genetic causes of heterotaxy, we analysed copy number variants (CNVs) in 225 patients with heterotaxy and heterotaxy-spectrum CHDs using array-based genotyping methods. Clinically relevant CNVs were identified in approximately 20% of patients and encompassed both known and putative heterotaxy genes. Patients were carefully phenotyped, revealing a significant association of abdominal situs inversus with pathogenic or likely pathogenic CNVs, while d-transposition of the great arteries was more frequently associated with common CNVs. Identified cytogenetic abnormalities ranged from large unbalanced translocations to smaller, kilobase-scale CNVs, including a rare, single exon deletion in ZIC3, a gene known to cause X-linked heterotaxy. Morpholino loss-of-function experiments in Xenopus support a role for one of these novel candidates, the platelet isoform of phosphofructokinase-1 ( PFKP ) in heterotaxy. Collectively, our results confirm a high CNV yield for array-based testing in patients with heterotaxy, and support use of CNV analysis for identification of novel biological processes relevant to human laterality. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

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