If the TP53 gene is damaged, tumor suppression is severely reduced. People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disease known as Li-Fraumeni syndrome.

An uncontrolled p53 protein ca induce apoptosis in neuronal cells and tigger neurodegenerative diseases.

•  Li-Fraumeni syndrome - Li-Fraumeni syndrome is a rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome.

SYMTOMS - Li-Fraumeni syndrome greatly increases susceptibility to cancer. The syndrome is linked to germline mutations of the p53 tumor suppressor gene. Persons with

LFS are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma

Fig: Showing various malingnancies

• Age of onset for cancers associated with Li-Fraumeni syndrome

Age of onset                                        Type of cancer

Infancy                                                 Development of adrenocortical carcinoma
Under five years of age                           Development of soft-tissue sarcomas 
Childhood and young adulthood               Acute leukemias and brain tumors
Adolescence                                          Osteosarcomas         
Twenties to thirties                                 Premenopausal breast cancer is common

PATHOLOGY:

•    LFS1: Mutations of TP53 prevent this normal function and allow damaged cells to divide and grow in an uncontrolled, unchecked manner forming tumors (cancers). TP53 mutations have been primarily implicated in Li-Fraumeni.
•    LFS2: A variant of Li-Fraumeni does not have a mutation in TP53 but instead has mutation of the CHEK2 (or CHK2) gene. CHK2 is also a tumor suppressor gene. The complete implication of this mutation is not known, but CHK2 regulates the action of p53.