Whole exome sequencing reveals a monogenic cause of disease in ∼43% of 35 families with Midaortic syndrome

Jillian K. Warejko, Markus Schueler, Asaf Vivante, Weizhen Tan, Ankana Daga, Jennifer A. Lawson, Daniela A. Braun, Shirlee Shril, Kassaundra Amann, Michael J.G. Somers, Nancy M. Rodig, Michelle A. Baum, Ghaleb Daouk, Avram Z. Traum, Heung Bae Kim, Khashayar Vakili, Diego Porras, James Lock, Michael J. Rivkin, Gulraiz ChaudryLeslie B. Smoot, Michael N. Singh, Edward R. Smith, Shrikant M. Mane, Richard P. Lifton, Deborah R. Stein, Michael A. Ferguson, Friedhelm Hildebrandt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Midaortic syndrome (MAS) is a rare cause of severe childhood hypertension characterized by narrowing of the abdominal aorta in children and is associated with extensive vascular disease. It may occur as part of a genetic syndrome, such as neurofibromatosis, or as consequence of a pathological inflammatory disease. However, most cases are considered idiopathic. We hypothesized that in a high percentage of these patients, a monogenic cause of disease may be detected by evaluating whole exome sequencing data for mutations in 1 of 38 candidate genes previously described to cause vasculopathy. We studied a cohort of 36 individuals from 35 different families with MAS by exome sequencing. In 15 of 35 families (42.9%), we detected likely causal dominant mutations. In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease (NF1, JAG1, ELN, GATA6, and RNF213). Ten of the 15 mutations have not previously been reported. This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS. Mutations were detected in NF1 (6/15 families), JAG1 (4/15 families), ELN (3/15 families), and one family each for GATA6 and RNF213. Eight individuals had syndromic disease and 7 individuals had isolated MAS. Whole exome sequencing can provide conclusive molecular genetic diagnosis in a high fraction of individuals with syndromic or isolated MAS. Establishing an etiologic diagnosis may reveal genotype/phenotype correlations for MAS in the future and should, therefore, be performed routinely in MAS.

Original languageEnglish
Pages (from-to)691-699
Number of pages9
Issue number4
StatePublished - 2018
Externally publishedYes


  • Aortic stenosis
  • Hypertension
  • Mutation
  • Neurofibromatoses
  • Whole exome sequencing


Dive into the research topics of 'Whole exome sequencing reveals a monogenic cause of disease in ∼43% of 35 families with Midaortic syndrome'. Together they form a unique fingerprint.

Cite this