SFMBT1 – Poland Syndrome

This summary evaluates the association between SFMBT1 and Poland syndrome. The evidence is derived from a single case report of a 14‑year‑old boy with Poland syndrome in which a heterozygous de novo pathogenic variant in SFMBT1 was identified. Notably, the case report provides both clinical observation and molecular investigation that demonstrate the pathogenic effect of the variant, specifically showing exon 10 skipping in SFMBT1 and a concomitant reduction in wild‑type protein levels (PMID:35483874).

Clinically, the association has been classified as Limited based on current evidence. Only one unrelated proband has been reported with a de novo variant supported by functional validation. Although familial segregation data are lacking, the de novo occurrence and biochemical confirmation provide preliminary credence to SFMBT1 as a gene contributing to the development of Poland syndrome (PMID:35483874).

Genetic evidence includes the identification of a de novo heterozygous variant in SFMBT1. Despite the small sample size (one proband), the variant, exemplified by c.772_790del (p.Ser258TrpfsTer39), is predicted to cause a loss‑of‑function effect through disruption of normal splicing. This finding is in line with an aberrant molecular mechanism that likely perturbs developmental processes critical to the formation of the pectoralis muscle (PMID:35483874).

Functional studies further support the association by demonstrating that the variant leads to exon 10 skipping, as confirmed by cDNA sequencing and western blot analysis. These experiments reveal a significant decrease in wild‑type SFMBT1 protein levels. The experimental data, while limited to this single case, align with the predicted deleterious effect and provide moderate evidence about the underlying pathogenic mechanism (PMID:35483874).

In summary, although additional cases and segregation analyses are needed to strengthen the evidence, the integration of de novo genetic occurrence with supportive functional assays substantiates an initial link between SFMBT1 and Poland syndrome. The current evaluation therefore warrants a classification of Limited evidence for this gene‑disease association.

Key Take‑home sentence: Despite the limited number of cases, the combined genetic and functional evidence supports a clinically actionable role for SFMBT1 in the etiology of Poland syndrome.

References

• Cold Spring Harbor Molecular Case Studies • 2022 • A de novo SFMBT1 pathogenic variant identified in a boy with Poland syndrome PMID:35483874

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