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Genetic evidence for LRIT3 in autosomal recessive complete congenital stationary night blindness (cCSNB) remains limited. In a molecular profiling of eight Indian families with cCSNB, no pathogenic LRIT3 variants were identified in any index patient or affected relatives (0 probands) (PMID:24715752). Consequently, no segregation data are available for LRIT3.
Functional studies provide moderate support for LRIT3 haploinsufficiency as the pathogenic mechanism. Lrit3 knockout mice harboring a premature stop codon exhibit a stationary “no b-wave” (nob) electroretinogram phenotype and thinning of the inner nuclear and plexiform retinal layers, mirroring human cCSNB findings (PMID:24598786). Subsequent investigations revealed mislocalization of TRPM1 and selective loss of mGluR6 cascade components at cone ON-bipolar cell dendritic tips in nob6 mice, demonstrating disrupted ON-pathway synaptic connectivity (PMID:28334377).
While concordant functional data support a role for LRIT3 in ON-bipolar cell signaling, the absence of confirmed LRIT3 variants in patient cohorts underscores the need for additional case reports and segregation analyses. Key Take-home: LRIT3 should be included in autosomal recessive cCSNB diagnostic panels, but further human genetic validation is required.
Gene–Disease AssociationLimitedNo LRIT3 probands identified in index cohort (0 probands) with no segregation data; functional concordance only Genetic EvidenceLimitedAbsence of reported LRIT3 variants in 8 families; no segregation or case reports provided Functional EvidenceModerateLrit3 knockout mouse recapitulates cCSNB ERG phenotype and retinal thinning; synaptic connectivity studies confirm disrupted ON-bipolar signaling |