Rapid detection by hydrops panel of Noonan syndrome with PTPN11 mutation (p.Thr73Ile) and persistent thrombocytopenia

Mol Genet Genomic Med. 2020 May;8(5):e1174. doi: 10.1002/mgg3.1174. Epub 2020 Mar 7.

Abstract

Background: Nonimmune hydrops fetalis (NIHF) is still a challenging diagnosis. The differential diagnosis is extensive and the success of identifying a cause depends on the thoroughness of efforts to establish a diagnosis. For the early diagnosis of NIHF, a virtual gene panel diagnostic tool was developed. The female premature baby in question was delivered via emergency cesarean at 30 + 1 weeks of gestational age (GA) due to rapidly developing NIHF to a healthy mother. The family history was noncontributory.

Methods: DNA of the family was extracted and sequenced by the virtual hydrops panel with whole-exome sequencing.

Results: The hydrops panel revealed Noonan syndrome (NS) with a germline mutation in PTPN11 c.218C>T (p.Thr73Ile).

Conclusion: The diagnosis of our patient was rapidly confirmed by the hydrops panel. The variant of c.218C>T (p.Thr73Ile) has not yet been described in literature relating to NIHF. Only a few case reports of this variant are known. This particular mutation is associated with Noonan syndrome, congenital heart defect and persistent thrombocytopenia. Few reveal juvenile myelomonocytic leukemia.

Keywords: hydrops panel; Noonan syndrome; next-generation sequencing; nonimmune hydrops fetalis; rare variant.

Publication types

  • Case Reports

MeSH terms

  • Exome Sequencing / methods
  • Female
  • Genetic Testing / methods
  • Humans
  • Hydrops Fetalis / diagnosis*
  • Hydrops Fetalis / genetics
  • Infant, Newborn
  • Mutation
  • Noonan Syndrome / diagnosis*
  • Noonan Syndrome / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / genetics

Substances

  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11