Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern

Matsuyama, Sho; Fukuda, Akihisa; Matsumoto, Atsushi; Eguchi, Hidetaka; Ueo, Taro; Ohana, Masaya; Seno, Hiroshi

doi:10.1007/s12328-023-01884-w

Cited by 1 publication

(1 citation statement)

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“…Matsuyama et al described the case of a 50 years old woman with gastric juvenile polyposis, who exhibited a nonsense variant in the SMAD4 gene at codon 169. The blood VAF was reported at 11%, and immunostaining of the resected specimen from total gastrectomy showed a partial loss of SMAD4 expression (Matsuyama et al, 2024). straightforward.…”

Section: Discussionmentioning

confidence: 98%

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

Vautier,

Mauillon,

Parodi

et al. 2024

American J of Med Genetics Pt A

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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.

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Section: Discussionmentioning

confidence: 98%