Rare copy number variants identified in prune belly syndrome

Nansi S. Boghossian, Robert J. Sicko, Andreas Giannakou, Aggeliki Dimopoulos, Michele Caggana, Michael Y Tsai, Edwina H. Yeung, Nathan D Pankratz, Benjamin R. Cole, Paul A. Romitti, Marilyn L. Browne, Ruzong Fan, Aiyi Liu, Denise M. Kay, James L. Mills

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare congenital disorder characterized by absence or hypoplasia of the abdominal wall musculature, urinary tract anomalies, and cryptorchidism in males. The etiology of PBS is largely unresolved, but genetic factors are implicated given its recurrence in families. We examined cases of PBS to identify novel pathogenic copy number variants (CNVs). A total of 34 cases (30 males and 4 females) with PBS identified from all live births in New York State (1998–2005) were genotyped using Illumina HumanOmni2.5 microarrays. CNVs were prioritized if they were absent from in-house controls, encompassed ≥10 consecutive probes, were ≥20 Kb in size, had ≤20% overlap with common variants in population reference controls, and had ≤20% overlap with any variant previously detected in other birth defect phenotypes screened in our laboratory. We identified 17 candidate autosomal CNVs; 10 cases each had one CNV and four cases each had two CNVs. The CNVs included a 158 Kb duplication at 4q22 that overlaps the BMPR1B gene; duplications of different sizes carried by two cases in the intron of STIM1 gene; a 67 Kb duplication 202 Kb downstream of the NOG gene, and a 1.34 Mb deletion including the MYOCD gene. The identified rare CNVs spanned genes involved in mesodermal, muscle, and urinary tract development and differentiation, which might help in elucidating the genetic contribution to PBS. We did not have parental DNA and cannot identify whether these CNVs were de novo or inherited. Further research on these CNVs, particularly BMP signaling is warranted to elucidate the pathogenesis of PBS.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalEuropean Journal of Medical Genetics
Issue number3
StatePublished - Mar 2018

Bibliographical note

Funding Information:
Grant sponsor: Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development ; Contract numbers: HHSN275201100001I , HHSN27500005 ; Grant sponsor: NICHD ; Contract number: N01-DK- 73431 ; Grant sponsor: National Human Genome Research Institute .

Funding Information:
We thank Natalie Weir at the Minnesota Core Laboratories and the staff at the Biomedical Genomics Center Facility at the University of Minnesota for microarray genotyping; Zoё L. Edmunds for assistance with qPCR assays and April J. Atkins, Emily C. McGrath, and Adam C. Gearhart for laboratory and technical assistance at the Wadsworth Center, New York State Department of Health; Sandra D. Richardson at the Congenital Malformations Registry, New York State Department of Health for data management; and Dr. Karl G. Hill with the Social Development Research Group (5R01DA024411) at the University of Washington for generously sharing population B allele frequency and GC content files for PennCNV software. This study makes use of data generated by the DECIPHER Consortium. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk . Funding for the DECIPHER project was provided by the Wellcome Trust . Those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation of it. Some data used for comparison in this manuscript were obtained from the ISCA Consortium database ( www.iscaconsortium.org ), which generates this information using NCBI's database of genomic structural variation (dbVar, www.ncbi.nlm.nih.gov/dbvar ), study nstd37. Samples and associated phenotype data were provided by ISCA Consortium member laboratories.


  • Abdominal wall musculature
  • Copy number variant
  • Eagle-barrett syndrome
  • Prune belly syndrome

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