Table 1.

Molecular Genetic Testing Used in Li-Fraumeni Syndrome

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
TP53 Sequence analysis 389% 4, 5
Gene-targeted deletion/duplication analysis 61% 7
Unknown 8NA
1.

See Table A. Genes and Databases for chromosome locus and protein.

2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.
5.

Sequence analysis of the entire TP53 coding region (exons 2-11) detects about 95% of TP53 pathogenic variants, most of which are missense variants.

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

7.

LFS can be caused by a deletion involving the coding region of TP53 or the promoter and noncoding exon [Guha & Malkin 2017].

8.

To date, TP53 is the only gene known to be associated with LFS. However, a germline pathogenic variant is detected in only 90% of individuals who meet classic LFS criteria and 50% of individuals who meet modified Chompret criteria [Bougeard et al 2015, Guha & Malkin 2017].

From: Li-Fraumeni Syndrome

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