Seminoma Caused by PDE11A Frameshift Variant with Multiple Abnormalities: A Case Report

Area of Science:

• Genetics
• Oncology
• Developmental Biology

Background:

• Testicular germ cell tumors (TGCTs) are rare malignancies primarily affecting young men.
• While cryptorchidism is a known risk factor, genetic predispositions are increasingly implicated in TGCT development.
• This case report investigates a patient with seminoma and multiple congenital abnormalities, exploring potential genetic underpinnings.

Observation:

• A 22-year-old male presented with varicocele, testicular pain, and a testicular nodule, diagnosed as seminoma.
• Further investigations revealed brain dysplasia, learning impairments, social challenges, and a presacral mass.
• Exome sequencing identified a frameshift variant in the PDE11A gene.

Findings:

• The identified PDE11A frameshift variant was predicted by AlphaFold3 to severely disrupt protein structure and function.
• This variant is hypothesized to play a pathogenic role in both the development of seminoma and associated systemic abnormalities.
• The patient experienced tumor recurrence, necessitating further treatment.

Implications:

• This case underscores the potential link between PDE11A gene variants and the pathogenesis of testicular cancer and related developmental issues.
• Advanced computational tools like AlphaFold3 are valuable for understanding the functional impact of genetic variants.
• Further research into PDE11A's role could improve diagnostic and therapeutic strategies for TGCTs and associated conditions.