Epidemiology of Surfactant Protein-B Deficiency - Full Text View

Purpose

The purpose of this study is to test the hypothesis that excess, rare, functionally disruptive single nucleotide polymorphisms (SNPs) characterize genes (e.g., the surfactant protein-B gene)(SFTPB) and gene networks (e.g., the pulmonary surfactant metabolic network) associated with increased risk of neonatal respiratory distress syndrome (RDS).

Condition
Lung Diseases Respiratory Distress Syndrome, Newborn Surfactant Deficiency

Study Type:	Observational [Patient Registry]
Study Design:	Observational Model: Case Control Time Perspective: Prospective
Target Follow-Up Duration:	4 Weeks
Official Title:	Epidemiology of Surfactant Protein-B Deficiency

Resource links provided by NLM:

Genetics Home Reference related topics: surfactant dysfunction

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

Statistical association of rare, functionally disruptive genomic variant with RDS [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Using custom exon capture, next generation sequencing, and in silico prediction of function, discover statistical associations between gene loci with excess, rare, functionally disruptive variants and risk of neonatal respiratory distress syndrome.

Secondary Outcome Measures:

Statistical associations between risk of neonatal respiratory distress syndrome and excess, rare functional variants in gene pathways [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Using custom exon capture, next generation sequencing, in silico prediction of functional variants, and Metacore for pathway construction, identify statistical associations between risk of neonatal respiratory distress syndrome and pathways with excess, rare functional variants

Biospecimen Retention: Samples With DNA

DNA and tracheal aspirate samples

Estimated Enrollment:	5000
Study Start Date:	June 2001
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts
I Descriptive cohort of population-based DNA samples from the newborn screening program in Missouri with vital statistics based, linked phenotype data
II Case-control cohort of infants with and without neonatal respiratory distress syndrome

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 1 Year
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Cohort I is a population-based cohort from Missouri. Cohort II is a case-control cohort from the Neonatal Intensive Care Unit at St. Louis Children's Hospital and from patients referred from other centers.

Criteria

Inclusion Criteria:

Normal pulmonary function or a diagnosis of RDS

Exclusion Criteria:

None

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014859

Locations

United States, Missouri
Washington University School of Medicine	Recruiting
St. Louis, Missouri, United States, 63110
Contact: F. Sessions Cole, MD 314-454-6148 cole@kids.wustl.edu

Sponsors and Collaborators

Washington University School of Medicine

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

F. Sessions Cole, MD

Washington University, St. Louis

More Information

Publications:

Hamvas A, Madden KK, Nogee LM, Trusgnich MA, Wegner DJ, Heins HB, Cole FS. Informed consent for genetic research. Arch Pediatr Adolesc Med. 2004 Jun;158(6):551-5.

Hamvas A, Wegner DJ, Trusgnich MA, Madden K, Heins H, Liu Y, Rice T, An P, Watkins-Torry J, Cole FS. Genetic variant characterization in intron 4 of the surfactant protein B gene. Hum Mutat. 2005 Nov;26(5):494-5.

Wilson RK, Ley TJ, Cole FS, Milbrandt JD, Clifton S, Fulton L, Fewell G, Minx P, Sun H, McLellan M, Pohl C, Mardis ER. Mutational profiling in the human genome. Cold Spring Harb Symp Quant Biol. 2003;68:23-9. Review. No abstract available.

Wegner DJ, Hertzberg T, Heins HB, Elmberger G, Maccoss MJ, Carlson CS, Nogee LM, Cole FS, Hamvas A. A major deletion in the surfactant protein-B gene causing lethal respiratory distress. Acta Paediatr. 2007 Apr;96(4):516-20.

Hamvas A, Wegner DJ, Carlson CS, Bergmann KR, Trusgnich MA, Fulton L, Kasai Y, An P, Mardis ER, Wilson RK, Cole FS. Comprehensive genetic variant discovery in the surfactant protein B gene. Pediatr Res. 2007 Aug;62(2):170-5.

Saugstad OD, Hansen TW, Rønnestad A, Nakstad B, Tølløfsrud PA, Reinholt F, Hamvas A, Coles FS, Dean M, Wert SE, Whitsett JA, Nogee LM. Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease. Acta Paediatr. 2007 Feb;96(2):185-90.

Garmany TH, Wambach JA, Heins HB, Watkins-Torry JM, Wegner DJ, Bennet K, An P, Land G, Saugstad OD, Henderson H, Nogee LM, Cole FS, Hamvas A. Population and disease-based prevalence of the common mutations associated with surfactant deficiency. Pediatr Res. 2008 Jun;63(6):645-9.

McBee AD, Wegner DJ, Carlson CS, Wambach JA, Yang P, Heins HB, Saugstad OD, Trusgnich MA, Watkins-Torry J, Nogee LM, Henderson H, Cole FS, Hamvas A. Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene. Pediatr Pulmonol. 2008 May;43(5):443-50.

Hamvas A, Heins HB, Guttentag SH, Wegner DJ, Trusgnich MA, Bennet KW, Yang P, Carlson CS, An P, Cole FS. Developmental and genetic regulation of human surfactant protein B in vivo. Neonatology. 2009;95(2):117-24. Epub 2008 Sep 6.

Druley TE, Vallania FL, Wegner DJ, Varley KE, Knowles OL, Bonds JA, Robison SW, Doniger SW, Hamvas A, Cole FS, Fay JC, Mitra RD. Quantification of rare allelic variants from pooled genomic DNA. Nat Methods. 2009 Apr;6(4):263-5. Epub 2009 Mar 1.

Hamvas A, Nogee LM, Wegner DJ, Depass K, Christodoulou J, Bennetts B, McQuade LR, Gray PH, Deterding RR, Carroll TR, Kammesheidt A, Kasch LM, Kulkarni S, Cole FS. Inherited surfactant deficiency caused by uniparental disomy of rare mutations in the surfactant protein-B and ATP binding cassette, subfamily a, member 3 genes. J Pediatr. 2009 Dec;155(6):854-859.e1. Epub 2009 Aug 3.

Anadkat JS, Kuzniewicz MW, Chaudhari BP, Cole FS, Hamvas A. Increased risk for respiratory distress among white, male, late preterm and term infants. J Perinatol. 2012 Oct;32(10):780-5. doi: 10.1038/jp.2011.191. Epub 2012 Jan 5.

Agrawal A, Hamvas A, Cole FS, Wambach JA, Wegner D, Coghill C, Harrison K, Nogee LM. An intronic ABCA3 mutation that is responsible for respiratory disease. Pediatr Res. 2012 Jun;71(6):633-7. doi: 10.1038/pr.2012.21. Epub 2012 Feb 15.

Bereman MS, Tomazela DM, Heins HS, Simonato M, Cogo PE, Hamvas A, Patterson BW, Cole FS, MacCoss MJ. A method to determine the kinetics of multiple proteins in human infants with respiratory distress syndrome. Anal Bioanal Chem. 2012 Jun;403(8):2397-402. doi: 10.1007/s00216-012-5953-3. Epub 2012 Apr 14.

Wambach JA, Wegner DJ, Depass K, Heins H, Druley TE, Mitra RD, An P, Zhang Q, Nogee LM, Cole FS, Hamvas A. Single ABCA3 mutations increase risk for neonatal respiratory distress syndrome. Pediatrics. 2012 Dec;130(6):e1575-82. doi: 10.1542/peds.2012-0918. Epub 2012 Nov 19.

Nogee LM. Abnormal expression of surfactant protein C and lung disease. Am J Respir Cell Mol Biol. 2002 Jun;26(6):641-4. No abstract available.

Merchak A, Janssen DJ, Bohlin K, Patterson BW, Zimmermann LJ, Carnielli VP, Hamvas A. Endogenous pulmonary surfactant metabolism is not affected by mode of ventilation in premature infants with respiratory distress syndrome. J Pediatr. 2002 Jun;140(6):693-8.

Cole FS. Surfactant protein B: unambiguously necessary for adult pulmonary function. Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L540-2. Review. No abstract available.

Nogee LM. Genetic mechanisms of surfactant deficiency. Biol Neonate. 2004;85(4):314-8. Epub 2004 Jun 08.

Hamvas A, Nogee LM, White FV, Schuler P, Hackett BP, Huddleston CB, Mendeloff EN, Hsu FF, Wert SE, Gonzales LW, Beers MF, Ballard PL. Progressive lung disease and surfactant dysfunction with a deletion in surfactant protein C gene. Am J Respir Cell Mol Biol. 2004 Jun;30(6):771-6. Epub 2003 Dec 04.

Cameron HS, Somaschini M, Carrera P, Hamvas A, Whitsett JA, Wert SE, Deutsch G, Nogee LM. A common mutation in the surfactant protein C gene associated with lung disease. J Pediatr. 2005 Mar;146(3):370-5.

Palomar LM, Nogee LM, Sweet SC, Huddleston CB, Cole FS, Hamvas A. Long-term outcomes after infant lung transplantation for surfactant protein B deficiency related to other causes of respiratory failure. J Pediatr. 2006 Oct;149(4):548-553.

Cole FS, Nogee LM, Hamvas A. Defects in Surfactant Synthesis: Clinical Implications. Pediatr Clin North Am. 2006 Oct;53(5):911-927. No abstract available.

Tomazela DM, Patterson BW, Hanson E, Spence KL, Kanion TB, Salinger DH, Vicini P, Barret H, Heins HB, Cole FS, Hamvas A, MacCoss MJ. Measurement of human surfactant protein-B turnover in vivo from tracheal aspirates using targeted proteomics. Anal Chem. 2010 Mar 15;82(6):2561-7.

Wambach JA, Yang P, Wegner DJ, An P, Hackett BP, Cole FS, Hamvas A. Surfactant protein-C promoter variants associated with neonatal respiratory distress syndrome reduce transcription. Pediatr Res. 2010 Sep;68(3):216-20.

Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00014859 History of Changes
Obsolete Identifiers:	NCT00200915
Other Study ID Numbers:	967, R01HL065174
Study First Received:	April 11, 2001
Last Updated:	April 22, 2013
Health Authority:	United States: Federal Government

Keywords provided by Washington University School of Medicine:

Pulmonary surfactant
Surfactant protein B
Surfactant protein C
ABCA3
NKX2-1

Additional relevant MeSH terms:

Lung Diseases
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Pulmonary Alveolar Proteinosis
Respiratory Tract Diseases
Respiration Disorders

Infant, Premature, Diseases
Infant, Newborn, Diseases
Pulmonary Surfactants
Respiratory System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013