There is abundant evidence published associating the PALB2 gene with Fanconi anemia complementation group N, since the gene-disease relationship was first proposed by Xia et al. (2007). Multiple case level studies have been performed with FA patients that have variants in the PALB2 gene. A significant amount of case-level data is available, however the maximum points for genetic evidence has been reached (12 points). BRCA1, BRCA2, BRIP1 and RAD51C have also been established as FA genes in the FA/BRCA DNA repair pathway. No full length PALB2 protein was detected in patient (EUFA1341)'s lymphoblasts and fibroblasts. The patients cells also show hypersensitivity to cross-linking agents and lacked BRCA2. Palb2-/-mouse model have been established to show consistent phenotypes with FA patients and Brca1 and Brca2 knockout mice including mesoderm differentiation defect and early embryonic lethality. Introduction of wild-type PALB2 into EUFA1341 fibroblasts cells normalized the association of BRCA2 with the chromatin/nuclear matrix fraction, the ability to form Rad51 foci and the sensitivity to MMC. PALB2 ∆ChAM did not rescue the sensitivity phenotype. All of these types of evidence are consistent with a definitive relationship between the PALB2 gene and Fanconi anemia complementation group N.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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