Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing

David J. Tester, Melissa L. Will, Carla M. Haglund, Michael John Ackerman

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

OBJECTIVES: The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS). BACKGROUND: Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test. METHODS: Blinded to genetic test results, analysis of the clinical phenotype was performed in 541 consecutive unrelated patients referred to Mayo Clinic's Sudden Death Genomics Laboratory for LQTS genetic testing from August 1997 to July 2004. RESULTS: The yield of genetic testing correlated significantly with the corrected QT interval (QTc) and clinical diagnostic score ranging from 0% when QTc was <400 ms to 62% when QTc was >480 ms (p < 0.0001). Among those with the highest clinical probability, the yield was 72% (89 of 123). The yield fluctuated substantially depending on age at diagnosis in males. Among physicians who referred <5 patients, the yield ranged from 0% to 80% (p < 0.0001). CONCLUSIONS: In this large cohort of unrelated patients referred for LQTS genetic testing, the clinical phenotype strongly correlated with the likelihood of elucidating a pathogenic mutation with the cardiac channel gene screen.

Original languageEnglish (US)
Pages (from-to)764-768
Number of pages5
JournalJournal of the American College of Cardiology
Volume47
Issue number4
DOIs
StatePublished - Feb 21 2006

Fingerprint

Long QT Syndrome
Genetic Testing
Phenotype
Molecular Pathology
Sudden Death
Genomics
Routine Diagnostic Tests
Genes
Genotype
Physicians
Mutation
Research

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing. / Tester, David J.; Will, Melissa L.; Haglund, Carla M.; Ackerman, Michael John.

In: Journal of the American College of Cardiology, Vol. 47, No. 4, 21.02.2006, p. 764-768.

Research output: Contribution to journalArticle

Tester, David J. ; Will, Melissa L. ; Haglund, Carla M. ; Ackerman, Michael John. / Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing. In: Journal of the American College of Cardiology. 2006 ; Vol. 47, No. 4. pp. 764-768.
@article{7d75396123ab461c81f7a244f8ec801b,
title = "Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing",
abstract = "OBJECTIVES: The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS). BACKGROUND: Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test. METHODS: Blinded to genetic test results, analysis of the clinical phenotype was performed in 541 consecutive unrelated patients referred to Mayo Clinic's Sudden Death Genomics Laboratory for LQTS genetic testing from August 1997 to July 2004. RESULTS: The yield of genetic testing correlated significantly with the corrected QT interval (QTc) and clinical diagnostic score ranging from 0{\%} when QTc was <400 ms to 62{\%} when QTc was >480 ms (p < 0.0001). Among those with the highest clinical probability, the yield was 72{\%} (89 of 123). The yield fluctuated substantially depending on age at diagnosis in males. Among physicians who referred <5 patients, the yield ranged from 0{\%} to 80{\%} (p < 0.0001). CONCLUSIONS: In this large cohort of unrelated patients referred for LQTS genetic testing, the clinical phenotype strongly correlated with the likelihood of elucidating a pathogenic mutation with the cardiac channel gene screen.",
author = "Tester, {David J.} and Will, {Melissa L.} and Haglund, {Carla M.} and Ackerman, {Michael John}",
year = "2006",
month = "2",
day = "21",
doi = "10.1016/j.jacc.2005.09.056",
language = "English (US)",
volume = "47",
pages = "764--768",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "4",

}

TY - JOUR

T1 - Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing

AU - Tester, David J.

AU - Will, Melissa L.

AU - Haglund, Carla M.

AU - Ackerman, Michael John

PY - 2006/2/21

Y1 - 2006/2/21

N2 - OBJECTIVES: The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS). BACKGROUND: Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test. METHODS: Blinded to genetic test results, analysis of the clinical phenotype was performed in 541 consecutive unrelated patients referred to Mayo Clinic's Sudden Death Genomics Laboratory for LQTS genetic testing from August 1997 to July 2004. RESULTS: The yield of genetic testing correlated significantly with the corrected QT interval (QTc) and clinical diagnostic score ranging from 0% when QTc was <400 ms to 62% when QTc was >480 ms (p < 0.0001). Among those with the highest clinical probability, the yield was 72% (89 of 123). The yield fluctuated substantially depending on age at diagnosis in males. Among physicians who referred <5 patients, the yield ranged from 0% to 80% (p < 0.0001). CONCLUSIONS: In this large cohort of unrelated patients referred for LQTS genetic testing, the clinical phenotype strongly correlated with the likelihood of elucidating a pathogenic mutation with the cardiac channel gene screen.

AB - OBJECTIVES: The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS). BACKGROUND: Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test. METHODS: Blinded to genetic test results, analysis of the clinical phenotype was performed in 541 consecutive unrelated patients referred to Mayo Clinic's Sudden Death Genomics Laboratory for LQTS genetic testing from August 1997 to July 2004. RESULTS: The yield of genetic testing correlated significantly with the corrected QT interval (QTc) and clinical diagnostic score ranging from 0% when QTc was <400 ms to 62% when QTc was >480 ms (p < 0.0001). Among those with the highest clinical probability, the yield was 72% (89 of 123). The yield fluctuated substantially depending on age at diagnosis in males. Among physicians who referred <5 patients, the yield ranged from 0% to 80% (p < 0.0001). CONCLUSIONS: In this large cohort of unrelated patients referred for LQTS genetic testing, the clinical phenotype strongly correlated with the likelihood of elucidating a pathogenic mutation with the cardiac channel gene screen.

UR - http://www.scopus.com/inward/record.url?scp=32644436410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32644436410&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2005.09.056

DO - 10.1016/j.jacc.2005.09.056

M3 - Article

C2 - 16487842

AN - SCOPUS:32644436410

VL - 47

SP - 764

EP - 768

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 4

ER -