Open AccessENG mutational mosaicism in a family with hereditary hemorrhagic telangiectasia
Author(s) -
Tørring Pernille M.,
Kjeldsen Anette D.,
Ousager Lilian Bomme,
Brusgaard Klaus
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.361
Subject(s) - sanger sequencing , proband , genetics , frameshift mutation , germline mosaicism , dna sequencing , biology , mutation , exon , heteroduplex , genetic counseling , medicine , gene
Abstract Background Hereditary hemorrhagic telangiectasia ( HHT ) is an autosomal dominant genetic disorder caused by mutations in ENG , ACVRL 1, or SMAD 4 . Around 90% of HHT patients present with a heterozygous pathogenic genetic variation. Almost all cases of HHT have a family history. Very few cases are de novo or mosaicism. We describe a case with mutational mosaicism that would not be observed in the clinical routine when using Sanger sequencing or a NGS read coverage below app. 100. Methods DNA was extracted from peripheral blood leukocytes, and buccal swabs. The coding region, exon–intron boundaries, and the flanking sequences of the genes were sequenced by NGS . Results The proband had clinical HHT fulfilling the Curaçao criteria and genetic testing identified a frameshift mutation in ENG . The mother of the proband, also with clinical HHT , was found negative when analyzing DNA from blood for the familial mutation using Sanger sequencing. Analyzing her DNA by NGS HHT panel sequencing when extracted from both peripheral blood leukocytes, and cheek swabs, identified the familial ENG mutation at low levels. Conclusion We provide evidence of ENG mutational mosaicism in an individual presenting with clinical HHT . These findings illustrate the importance of considering mutational mosaicism.