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.