GTS5:PALB2-related cancer predisposition syndrome (PALB2): Difference between revisions

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 Put your text here <span style="color:#0070C0">(''Instructions: Include a brief general clinical description, diagnostic criteria, and differential diagnosis if applicable. Include disease context relative to other WHO classification categories, i.e. describe any information relevant to the genetic aspects of the disease from all WHO classification books in which the syndrome is described.'')</span>
-- Function: The ''PALB2'' gene at 16p12.2 contains 13 exons encoding 1,186 amino acids. The PALB2 protein is a component of the homologous recombination complex machinery that binds to the BRCA2 protein to repair double-strand DNA breaks. PALB2 functions as a tumor-suppressor to maintain genome integrity.
+== PALB2 – Gene Function and Clinical Relevance ==
-- In the heterozygous state, germline pathogenic variants in PALB2 predispose carriers to several cancers, commonly including breast, pancreatic, and ovarian cancers, with incomplete penetrance for these cancers. Germline pathogenic variants in PALB2 have also been reported in individuals with prostate, gastric, and colon cancers.
+=== Gene Function ===
+The PALB2 gene is located at chromosome 16p12.2 and contains 13 exons, encoding a 1,186 amino acid protein. PALB2 (Partner and Localizer of BRCA2) is a key component of the homologous recombination (HR) DNA repair pathway, where it directly interacts with BRCA2 to facilitate the accurate repair of DNA double-strand breaks. Through its role in DNA damage repair, PALB2 functions as a tumor suppressor that maintains genomic integrity<ref name=":0" /><ref name=":1" />
-- In the compound heterozygous or homozygous state, biallelic pathogenic variants in PALB2 cause Fanconi anemia (FA) subtype N (Complementation Group N - FANCN), which is a severe genomic instability condition characterized by growth retardation, congenital malformations, skeletal abnormalities, hearing loss, intellectual disability, progressive bone marrow failure, anemia, and pediatric cancer susceptibility (acute leukemia in early childhood).
-- Incidence: 0.1%
-- Heterozygous pathogenic variants in PALB2 are associated with a 33-53% risk for breast cancer and an increased risk for pancreatic and ovarian cancers.
-- Lifetime risk of breast cancer in females is 35-60% (relative risk ~ 5-fold). The incidence of triple negative breast cancer is enriched in those with PALB2-related breast cancer.
 === PALB2 Related Cancer Predisposition Syndrome: ===