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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.

Titel:	SMAD4 mosaicism in juvenile polyposis: Essential contribution of somatic analysis in diagnosis.
Autor/in / Beteiligte Person:	Vautier, S ; Mauillon, J ; Parodi, N ; Bou, J ; Kasper, E ; Manase, S ; Houdayer, C ; Baert-Desurmont, S
Zeitschrift:	American journal of medical genetics. Part A, 2024-05-02, S. e63648
Veröffentlichung:	Ahead of Print, 2024
Medientyp:	report
ISSN:	1552-4833 (electronic)
DOI:	10.1002/ajmg.a.63648
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Contributed Indexing: Keywords: Mosaicism; SMAD4; juvenile polyposis syndrome Entry Date(s): Date Created: 20240502 Latest Revision: 20240502 Update Code: 20240502

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