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Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond–Blackfan anaemia
  1. Margaret J Wat1,
  2. Victoria B Enciso1,
  3. Wojciech Wiszniewski1,
  4. Trevor Resnick3,
  5. Patricia Bader4,
  6. Elizabeth R Roeder5,
  7. Debra Freedenberg6,7,
  8. Chester Brown1,2,
  9. Pawel Stankiewicz1,8,
  10. Sau-Wai Cheung1,
  11. Daryl A Scott1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  2. 2Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
  3. 3Department of Neurology, Miami Children's Hospital and University of Miami, Miami, Florida, USA
  4. 4Northeast Indiana Genetic Counseling Center, Parkview Hospital, Fort Wayne, Indiana, USA
  5. 5Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA
  6. 6Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennesee, USA
  7. 7Department of State Health Services, Austin, Texas, USA
  8. 8Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
  1. Correspondence to Daryl A Scott, Department of Pediatrics, Baylor College of Medicine, Houston, R813, One Baylor Plaza, BCM 227, Houston, TX 77030, USA; dscott{at}


Background Congenital diaphragmatic hernia (CDH) can occur in isolation or in association with other abnormalities. We hypothesised that some cases of non-isolated CDH are caused by novel genomic disorders.

Methods and results In a cohort of >12 000 patients referred for array comparative genomic hybridisation testing, we identified three individuals—two of whom had CDH—with deletions involving a ∼2.3 Mb region on chromosome 15q25.2. Two additional patients with deletions of this region have been reported, including a fetus with CDH. Clinical data from these patients suggest that recurrent deletions of 15q25.2 are associated with an increased risk of developing CDH, cognitive deficits, cryptorchidism, short stature and possibly Diamond–Blackfan anaemia (DBA). Although no known CDH-associated genes are located on 15q25.2, four genes in this region—CPEB1, AP3B2, HOMER2 and HDGFRP3—have been implicated in CNS development/function and may contribute to the cognitive deficits seen in deletion patients. Deletions of RPS17 may also predispose individuals with 15q25.2 deletions to DBA and associated anomalies.

Conclusions Individuals with recurrent deletions of 15q25.2 are at increased risk for CDH and other birth defects. A high index of suspicion should exist for the development of cognitive defects, anaemia and DBA-associated malignancies in these individuals.

  • Congenital diaphragmatic hernia
  • microdeletion
  • 15q25.2
  • Diamond-Blackfan anaemia
  • RPS17
  • clinical genetics
  • cytogentics
  • molecular genetics
  • haematology (incl blood transfusion)
  • other respiratory medicine

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  • Funding NIH; Polish Ministry of Science and Higher Education.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Baylor College of Medicine Institutional Review Board (IRB), Houston, TX 77030, USA.

  • Provenance and peer review Not commissioned; externally peer reviewed.