INVS – Senior-Loken syndrome

Inversin (INVS) encodes a ciliary protein essential for renal development and has been implicated in infantile nephronophthisis. Biallelic truncating and splice variants such as c.1789C>T (p.Arg597Ter) cause early-onset nephronophthisis, but comprehensive screening of Senior-Loken syndrome cohorts has not identified causative INVS variants, yielding zero probands and no segregation data. This absence of genetic findings in SLSN panels indicates a lack of direct clinical evidence connecting INVS to retinal manifestations.

Functional analyses reveal that INVERSIN can bind RNA and localize to stress granules upon translational inhibition (PMID:32994509), and mechanistic studies demonstrate INVERSIN regulates cortical actin dynamics and spindle positioning during mitosis, impacting nephron morphogenesis (PMID:23515530). These experiments support a general ciliopathy role but do not confirm a retinal phenotype in SLSN. Additional genetic and phenotypic studies are required to elucidate any potential contribution of INVS to Senior-Loken syndrome.

Key Take-home: While INVS is established in nephronophthisis, current data provide limited support for its role in Senior-Loken syndrome; inclusion in genetic testing panels should be interpreted cautiously.

References

• Gene • 2020 • Novel splice site and nonsense variants in INVS cause infantile nephronophthisis. PMID:31706999
• Scientific reports • 2020 • Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules. PMID:32994509
• American journal of physiology. Cell physiology • 2013 • Inversin modulates the cortical actin network during mitosis. PMID:23515530

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