ENG mutational mosaicism in a family with hereditary hemorrhagic telangiectasia

被引:15
作者
Torring, Pernille M. [1 ]
Kjeldsen, Anette D. [2 ]
Ousager, Lilian Bomme [1 ]
Brusgaard, Klaus [1 ]
机构
[1] Odense Univ Hosp, Dept Clin Genet, Odense C, Denmark
[2] Odense Univ Hosp, Dept Otorhinolaryngol, Odense, Denmark
来源
MOLECULAR GENETICS & GENOMIC MEDICINE | 2018年 / 6卷 / 01期
关键词
ENG; genetic testing; hereditary hemorrhagic telangiectasia; HHT; mosaic; mosaicism; mutational mosaicism; SMAD4; HHT;
D O I
10.1002/mgg3.361
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder caused by mutations in ENG, ACVRL1, or SMAD4. 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 Curacao 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.
引用
收藏
页码:121 / 125
页数:5
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