Poster Presentations

PTPN11, SOS1, and BRAF Gene Mutation Spectrum in RASopathies in Molecular Diagnosis

  • Semih Aşıkovalı
  • Ayça Aykut
  • Asude Durmaz
  • Hüseyin Onay
  • Filiz Hazan
  • Samim Özen
  • Tahir Atik
  • Cengiz Kara
  • Erhan Mihçi
  • Damla Gökşen

J Clin Res Pediatr Endocrinol 2017;9(1):25-25

RASopathy is a group of clinically defined medical genetic syndromes that are caused by germline mutations in genes encoding the Ras/mitogen-activated protein kinase (MAPK) pathway components or regulators. Noonan, LEOPARD, cardio-phasio-cutaneous, Costello, Legius syndrome, and neurofibromatosis type 1 are included in this group. The aim of this study was to evaluate the PTPN11, SOS1, and BRAF gene mutation spectrum of 70 patients with molecular diagnosis upon the prediagnosis of CFC and Noonan syndrome in RASopathy spectrum between 2008 and 2016 in Ege University Medical Faculty Medical Genetics Department.

Sequence analysis was performed on all coding exons and flanking intronic regions of the PTPN11 gene, exons 6, 7, 8, 10, and 16 of SOS1 gene, and exons 6, 11, 12, 14, and 15 of BRAF gene in 403 cases referred with prediagnosis of RASopathy between 2010 and 2016. Sanger sequencing analysis method was used for sequence analysis.

Mutations were detected in seventy of the cases (17%). In 63 cases, 28 different mutations were detected in the PTPN11 gene. The frequency rates of PTPN11 mutation in this study were as follows: p.N308D (26%), p.Y63C (6%), p.I282V (5%), p.M504V (5%), p.T468M (5%), and p.Y62D (5%). In 4 cases, 3 different mutations were detected in the SOS1 gene. Mutations were identified as p.R522K, p.I600V, and p.E846K. In 3 cases, 3 different mutations were detected in the BRAF gene. Mutations were identified as p.E501K, p.N581D, and p.A481E.

In our study, we presented the largest RASopathy mutation spectrum in Turkey to date and we demonstrated that the mutation spectrum is also highly heterogeneous in these clinically heterogeneous group diseases.