CLN3 – Inherited Retinal Dystrophy

Juvenile neuronal ceroid lipofuscinosis gene CLN3 has been implicated in retinal degeneration beyond its classical Batten disease phenotype. In a cohort of 30 unrelated Mexican patients with inherited retinal dystrophy, exome sequencing coupled with read-depth CNV analysis identified pathogenic or likely pathogenic CLN3 copy number variants in 2 probands (PMID:39400524). This autosomal recessive finding expands the phenotypic spectrum of CLN3 to include non-syndromic retinal dystrophy and underscores the importance of structural variant detection in genetically unresolved cases.

Genetic evidence remains limited: only 2 probands with biallelic CLN3 structural variants have been reported and no segregation data are available. One of the detected variants is c.1213C>T (p.Arg405Trp), a missense change consistent with loss of function in a recessive model. There are no direct functional studies of these CLN3 variants in retinal models, and the pathogenic mechanism in photoreceptors awaits elucidation. Inclusion of CNV analysis should be routine in negative exome or panel testing for inherited retinal dystrophy to improve diagnostic yield.

References

• Pathogenic copy number variants in inherited retinal dystrophy PMID:39400524

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