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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark. pernille.toerring@ouh.regionsyddanmark.dk
authors.forename: Pernille M
authors.initials: PM
authors.lastname: Tørring
authors.forename: Anette D
authors.initials: AD
authors.lastname: Kjeldsen
authors.forename: Lilian Bomme
authors.initials: LB
authors.lastname: Ousager
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brasch-Andersen
authors.forename: Klaus
authors.initials: K
authors.lastname: Brusgaard
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D000071063:Endoglin; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics*; D051901:Smad4 Protein / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II