Homozygous TP53 alterations: a case of a biallelic splice variant and a brief review of the literature.

Biallelic germline variants in TP53 are exceedingly rare, and their clinical consequences remain poorly defined. Here, we report a female infant born to consanguineous parents who presented with early-onset, aggressive choroid plexus carcinoma causing death at age 4. Molecular analysis identified a homozygous synonymous variant in the last nucleotide of exon 4 in TP53 (NM_000546.6:c.375G > A, p.Thr125 =). This variant has been previously shown to cause aberrant splicing and partial loss of p53 function, and has been associated with variable penetrance in heterozygous carriers. Both parents, who were first cousins, were heterozygous carriers, and no malignancy history was present at the time of diagnosis. Following identification of carrier status, the couple underwent preimplantation genetic testing and subsequently had a child who did not inherit the familial TP53 variant. This report represents one of the very few documented cases of biallelic TP53 variants and underscores the phenotypic heterogeneity associated with TP53 homozygosity. The case highlights the importance of genetic evaluation in pediatric patients with rare aggressive tumors, particularly in consanguineous families, and demonstrates the critical role of genetic counseling and surveillance in affected relatives.