Identification of a novel germ-line mutation in the TP53 gene in a Mexican family with Li-Fraumeni syndrome.
BACKGROUND
Germ-line mutations of the TP53 gene are known to cause Li-Fraumeni syndrome, an autosomal, dominantly inherited, high-penetrance cancer-predisposition syndrome characterized by the occurrence of a variety of cancers, mainly soft tissue sarcomas, adrenocortical carcinoma, leukemia, breast cancer, and brain tumors.


METHODS
Mutation analysis was based on Denaturing high performance liquid chromatography (DHPLC) screening of exons 2-11 of the TP53 gene, sequencing, and cloning of DNA obtained from peripheral blood lymphocytes.


RESULTS
We report herein on Li Fraumeni syndrome in a family whose members are carriers of a novel TP53 gene mutation at exon 4. The mutation comprises an insertion/duplication of seven nucleotides affecting codon 110 and generating a new nucleotide sequence and a premature stop codon at position 150. With this mutation, the p53 protein that should be translated lacks the majority of the DNA binding domain.


CONCLUSIONS
To our knowledge, this specific alteration has not been reported previously, but we believe it is the cause of the Li-Fraumeni syndrome in this family.
Taja-Chayeb
Lucia
L
Instituto Nacional de Cancerología (INCan), Mexico City, México. ltaja_chayeb@yahoo.com
Vidal-Millán
Silvia
S
Gutiérrez-Hernández
Olga
O
Trejo-Becerril
Catalina
C
Pérez-Cárdenas
Enrique
E
Chávez-Blanco
Alma
A
de la Cruz-Hernández
Erick
E
Dueñas-González
Alfonso
A
D000328:Adult; D000368:Aged; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010375:Pedigree; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
D017931:DNA Primers; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53