Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia

Joanne S. Chiu, Lijiang Ma, Julia Wynn, Usha Krishnan, Erika B. Rosenzweig, Gudrun Aspelund, Marc Arkovitz, Brad W. Warner, Foong Yen Lim, George B. Mychaliska, Kenneth Azarow, Robert A. Cusick, Dai H. Chung, Wendy K. Chung

Research output: Research - peer-reviewArticle

Abstract

Background: Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Methods: Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3. months of age; moderate of severe PH at 1. month of age with death occurring prior to the 3. month echocardiogram; or on PH medications at 1. month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations. Results: There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes. Type of study: Prognosis study. Level of evidence: Level IV.

LanguageEnglish (US)
JournalJournal of Pediatric Surgery
DOIs
StateAccepted/In press - Nov 4 2016

Fingerprint

Pulmonary Hypertension
Mutation
Congenital Diaphragmatic Hernias
Caveolin 1
Mortality
Genes
Type II Bone Morphogenetic Protein Receptors
Diaphragmatic Hernia
DNA Sequence Analysis
Echocardiography
Newborn Infant
Prospective Studies
Morbidity
Lung
Research
potassium channel subfamily K member 3

Keywords

  • BMPR2
  • CAV1
  • Congenital diaphragmatic hernia
  • KCNK3
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Cite this

Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia. / Chiu, Joanne S.; Ma, Lijiang; Wynn, Julia; Krishnan, Usha; Rosenzweig, Erika B.; Aspelund, Gudrun; Arkovitz, Marc; Warner, Brad W.; Lim, Foong Yen; Mychaliska, George B.; Azarow, Kenneth; Cusick, Robert A.; Chung, Dai H.; Chung, Wendy K.

In: Journal of Pediatric Surgery, 04.11.2016.

Research output: Research - peer-reviewArticle

Chiu, JS, Ma, L, Wynn, J, Krishnan, U, Rosenzweig, EB, Aspelund, G, Arkovitz, M, Warner, BW, Lim, FY, Mychaliska, GB, Azarow, K, Cusick, RA, Chung, DH & Chung, WK 2016, 'Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia' Journal of Pediatric Surgery. DOI: 10.1016/j.jpedsurg.2017.01.007
Chiu, Joanne S. ; Ma, Lijiang ; Wynn, Julia ; Krishnan, Usha ; Rosenzweig, Erika B. ; Aspelund, Gudrun ; Arkovitz, Marc ; Warner, Brad W. ; Lim, Foong Yen ; Mychaliska, George B. ; Azarow, Kenneth ; Cusick, Robert A. ; Chung, Dai H. ; Chung, Wendy K./ Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia. In: Journal of Pediatric Surgery. 2016
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AU - Chiu,Joanne S.

AU - Ma,Lijiang

AU - Wynn,Julia

AU - Krishnan,Usha

AU - Rosenzweig,Erika B.

AU - Aspelund,Gudrun

AU - Arkovitz,Marc

AU - Warner,Brad W.

AU - Lim,Foong Yen

AU - Mychaliska,George B.

AU - Azarow,Kenneth

AU - Cusick,Robert A.

AU - Chung,Dai H.

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AB - Background: Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Methods: Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3. months of age; moderate of severe PH at 1. month of age with death occurring prior to the 3. month echocardiogram; or on PH medications at 1. month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations. Results: There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes. Type of study: Prognosis study. Level of evidence: Level IV.

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