SAMD7 – Retinitis Pigmentosa

This summary reviews the association between SAMD7 (HGNC:25394) and retinitis pigmentosa (MONDO_0019200) based on the currently available evidence. In a consanguineous Turkish family, 2 affected siblings were identified with an unusual retinitis pigmentosa phenotype, where in addition to a homozygous coding mutation in RHO, non‑coding homozygous variants were found in two SAMD7 regulatory regions (PMID:26887858). Although these SAMD7 variants do not alter the protein coding sequence, functional in vitro assays demonstrated decreased transcriptional activity in reporter constructs, suggesting a cis‑regulatory mechanism that impacts SAMD7 expression and retinal function.

Genetic evidence for SAMD7 is limited, as no coding mutations were reported and the only variants noted affect non‑coding regulatory elements. The study identified these variants solely in a single family with 2 affected probands (PMID:26887858), and no additional segregation data from unrelated families was provided. This restricts the genetic evidence to a limited level despite supportive experimental data.

Autosomal recessive inheritance is observed in the affected family, with the SAMD7 regulatory variants segregating alongside the retinitis pigmentosa phenotype. Although the presence of a homozygous pathogenic variant in the RHO gene complicates the genetic landscape, the altered SAMD7 expression pattern may contribute to the unusual pigment deposit presentation observed in these patients. The limited number of probands and the absence of independently replicated coding mutations in SAMD7 reduce the overall genetic evidence score.

Functional evidence, however, is bolstered by robust experimental assessments. Luciferase reporter assays and retinal explant electroporations demonstrated that the non‑coding variants in SAMD7 lead to a significant decrease in transcriptional activity (PMID:26887858). These results indicate a plausible cis‑regulatory mechanism whereby altered SAMD7 expression could modulate the retinal phenotype, underscoring the biological relevance of SAMD7 in retinal physiology.

While the primary data linking SAMD7 to retinitis pigmentosa comes from this single consanguineous family, additional functional studies support its role in retinal pathology. Further investigations, including larger cohorts and independent replication, are necessary to confirm the genetic association and fully elucidate the contribution of SAMD7 dysregulation to disease etiology. In contrast, an independent study identified SAMD7 mutations in autosomal-recessive macular dystrophy (PMID:38272031), further underscoring the gene’s importance in retinal disorders even though the phenotype differs from classic retinitis pigmentosa.

Key take‑home message: Despite limited genetic evidence based on a single family, functional experiments provide moderate support for a cis‑regulatory mechanism impacting SAMD7 expression and retinal function, making it a candidate gene of clinical interest in atypical presentations of retinitis pigmentosa.

References

• Scientific Reports • 2016 • Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non‑coding cis‑regulatory variants in CRX‑binding regions of SAMD7 PMID:26887858
• American Journal of Human Genetics • 2024 • Mutations in SAMD7 cause autosomal‑recessive macular dystrophy with or without cone dysfunction PMID:38272031

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