case_images: PMC11327130_01
case_images: Family tree. The proband is indicated with an arrow (III_10). Melanoma cases are reported in the father (II-5), sister (III-11), and paternal aunt (II-2). The mother (II-6) has been reported to have a not well-defined "skin cancer." In the family, other cancer types are present: breast cancer (BC; II-9, III-9), lung cancer (III-11), gastric cancer (III-19, I-4), colorectal cancer (CRC, II-1), and thyroid cancer (III-11, III-4).
case_images: fonc-14-1419739-g001.jpg
case_images: PMC11327130_01_fonc-14-1419739-g001.jpg
case_images: f1
case_images: Examination of familial history also pointed to a possible genetic syndrome of oncological predisposition ( Figure 1 ), given the cases of melanoma in the patient's sister (III-11), paternal aunt (II-2), and father (II-5), coupled with an indistinct skin condition in the mother (II-6), referred to as "skin tumors" that had not been well characterized.
case_images: IGV screenshot and Sanger sequencing. On the top, the IGV screenshot is depicted (A), showing the variant R363* in POT1, in a heterozygous state, identified in the NGS analyses. On the bottom, an electropherogram of Sanger sequencing confirms the NGS results (B).
case_images: fonc-14-1419739-g002.jpg
case_images: PMC11327130_01_fonc-14-1419739-g002.jpg
case_images: f2
case_images: The alteration was confirmed by Sanger sequencing ( Figure 2 ). This variant is present on the gnomAD database, with a maximum subpopulation frequency of 0.0047% in the European (non-Finnish) population (7-124482937-G-A, gnomAD v2.1.1, gnomad.broadinstitute.com).
case_images: Segregation analysis for the POT1 variant R363*. The proband is indicated with an arrow. In the father, daughter, and son, segregation analysis by Sanger sequencing was performed. The daughter, who was positive for the POT1 variant, underwent exportation of two basal cell carcinoma after the test.
case_images: fonc-14-1419739-g003.jpg
case_images: PMC11327130_01_fonc-14-1419739-g003.jpg
case_images: f3
case_images: The daughter (IV-3), 32 years old, is the sole family member who tested positive for the POT1 variant ( Figure 3 ) and had two suspected lesions that were removed from the right side and the back after both were identified as basal cell carcinoma.