Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

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Resumé

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies. © Copyright 2012, Mary Ann Liebert, Inc.
OriginalsprogEngelsk
TidsskriftGenetic Testing and Molecular Biomarkers
Vol/bind16
Udgave nummer12
Sider (fra-til)1419-1423
Antal sider5
ISSN1945-0265
DOI
StatusUdgivet - 1. dec. 2012

Fingeraftryk

Mutation
Haplotypes
Sequence Analysis

Citer dette

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title = "Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia",
abstract = "Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies. {\circledC} Copyright 2012, Mary Ann Liebert, Inc.",
author = "T{\o}rring, {Pernille M} and A.D. Kjeldsen and L.B. Ousager and C. Brasch-Andersen and K. Brusgaard",
year = "2012",
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language = "English",
volume = "16",
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Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia. / Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.; Brasch-Andersen, C.; Brusgaard, K.

I: Genetic Testing and Molecular Biomarkers, Bind 16, Nr. 12, 01.12.2012, s. 1419-1423.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

AU - Tørring, Pernille M

AU - Kjeldsen, A.D.

AU - Ousager, L.B.

AU - Brasch-Andersen, C.

AU - Brusgaard, K.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies. © Copyright 2012, Mary Ann Liebert, Inc.

AB - Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies. © Copyright 2012, Mary Ann Liebert, Inc.

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DO - 10.1089/gtmb.2012.0230

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