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Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA‐binding site in an adolescent with two primary sarcomas
Author(s) -
Austin Frances,
Oyarbide Usua,
Massey Gita,
Grimes Margaret,
Corey Seth J.
Publication year - 2017
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26584
Subject(s) - genetics , germline mutation , germline , splice site mutation , splice , mutation , dna , binding site , biology , rna splicing , medicine , gene , rna
Pathologic variants in TP53 are known risk factors for the development of cancer. We report a 17‐year‐old male who presented with two primary sarcomas. Germline sequencing revealed a novel TP53 c.672 G>A mutation. Sequencing revealed wild‐type TP53 in the parents, and there was no history of cancer in first‐degree relatives. This de novo synonymous germline mutation results in a 5′ cryptic splice site that is bound by U1, resulting in a shift of the splice site by 5 base pairs. The frame shift results in a truncated protein at residue 246, which disrupts the DNA‐binding domain of p53.