Details

Autor(en) / Beteiligte

• Vautier, Sabine
• Mauillon, Jacques
• Parodi, Nathalie
• Bou, Jacqueline
• Kasper, Edwige
• Manase, Sandrine
• Houdayer, Claude
• Baert-Desurmont, Stéphanie

Titel

SMAD4 mosaicism in juvenile polyposis: Essential contribution of somatic analysis in diagnosis

Ist Teil von

• American journal of medical genetics. Part A, 2024-05, p.e63648

Ort / Verlag

United States

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Wiley Online Library - Journals

Beschreibungen/Notizen

• Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps in the gastrointestinal tract, associated with pathogenic variants of BMPR1A and SMAD4. We present the description of SMAD4 mosaicism in a 30-year-old man who had caecum adenocarcinoma, 11 juvenile colon polyps and epistaxis since childhood. We conducted NGS polyposis and CRC panel analysis on DNA extracted from two polyps, revealing a likely pathogenic SMAD4 variant: NM_005359.5:c. 1600C>T, p.(Gln534*). This variant was then identified at a very low frequency on blood and normal colonic tissue, by targeted visualization of previously obtained NGS data. These findings support the presence of a likely pathogenic mosaic SMAD4 variant that aligns with the patient's phenotype. Given the relatively frequent occurrence of de novo SMAD4 mutations, somatic mosaicism could account for a significant proportion of sporadic JPS patients with unidentified pathogenic variants. This case underscores the diagnosis challenge of detecting mosaicism and emphasizes the importance of somatic analyses.