In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii471-iii471
Abstract:
Germ line gain-of-function mutations in several members of the RAS/MAPK pathway, including PTPN11 are associated with signalopathies named Rasopathies and known as Noonan syndrome and closely related conditions. Patients harboring Rasopathies are at increased risk of myeloproliferative diseases and solid tumors, such as neuroblastoma. Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, represent the second most frequent genetic defect in Rasopathies. However, SOS1 mutations are rare in human malignancies and patients with germline SOS1 mutations may not be at increased risk of developing cancer. Here, we report a SOS1 variant found to segregate in a Tunisian pedigree with many members affected by brain tumors as well as epileptic disorder. During our genetic counselling for congenital heart diseases, a 9-year-old female born at Sfax from a consanguineous couple and having pulmonic valvular stenosis, has been investigated at the molecular level. Screening of mutations in the entire coding sequence of PTPN11, Braf and SOS1, was conducted using HRM analysis and bidirectional sequencing. Heterozygous single nucleotide substitution of SOS1 gene: c.1655 G & gt;A was confirmed. This mutation affected the PH-REM linker domain with substitution of residue Arg552 to Lys: p.Arg552Lys. This mutation accounts for one-third of all mutations reported in SOS1 during Rasopathies. Although no other molecular exploration was done, family history revealed other affected children by neurodevelopmental and epileptic conditions as well as recurrent brain malignancies in the paternal family. Two aunts developed blindness and then died subsequently to tumor progression.
Type of Medium:
Online Resource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa222.850
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2094060-9
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