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This summary reviews the association between LRFN5 (HGNC:20360) and autism spectrum disorder (MONDO_0005258) based on a case report and multi‐patient studies. In a detailed case report, a 16‑year‑old male with autism spectrum disorder was found to carry a microdeletion affecting the pseudogene chr14.232.a, which in turn significantly decreased LRFN5 expression in patient fibroblasts. Functional experiments demonstrated that transfection with a plasmid expressing chr14.232.a restored LRFN5 levels, while siRNA knockdown of the pseudogene further reduced its expression (PMID:31152157).
A multi‑patient study further supports the potential involvement of LRFN5 in neurodevelopmental phenotypes. In a cohort of approximately 1,200 patients undergoing clinical array CGH testing, eight patients were found to harbor small deletions encompassing LRFN5 along with other critical neurodevelopmental genes, linking these CNVs to variable presentations including autism spectrum disorder (PMID:22031302).
The genetic evidence comprises the single case report with a microdeletion and additional CNV observations involving LRFN5. Although the absolute number of probands for LRFN5 is limited—with one proband from the case report (PMID:31152157) and eight additional cases reported in a cohort setting (PMID:22031302)—this data provides preliminary support for a role of LRFN5 in autism spectrum disorder.
The functional evidence is robust. Patient fibroblast studies confirmed that loss of the pseudogene product significantly impairs LRFN5 expression. Importantly, rescue experiments via transfection indicate a direct functional relationship between the deleted pseudogene and LRFN5 expression, supporting a model of haploinsufficiency contributing to ASD pathogenesis (PMID:31152157).
No clear familial segregation or additional affected relative data was provided in the available reports; thus, segregation evidence remains minimal. Inheritance appears to be sporadic with the deletions most likely acting in an autosomal dominant manner given the haploinsufficiency observed.
In summary, while genetic evidence directly linking LRFN5 to autism spectrum disorder is limited by small proband numbers, strong functional assays provide important insights into the gene’s role in neural development. Additional large‐scale studies are required to surpass current evidence caps; however, this association offers a promising candidate for diagnostic decision‑making and potential targeted therapeutic exploration.
Key Take‑home: Comprehensive evaluation of LRFN5 alterations—including both genetic and functional data—provides a preliminary, yet valuable, framework for its consideration in the molecular diagnosis of autism spectrum disorder.
Gene–Disease AssociationLimitedA single case report with a microdeletion (PMID:31152157) coupled with additional CNV findings in eight patients from a large cohort (PMID:22031302) supports a limited gene‐disease association. Genetic EvidenceLimitedGenetic findings are derived from one detailed case and several CNV cases, yielding a modest number of probands (1 proband PMID:31152157 and 8 cases PMID:22031302) without extensive familial segregation data. Functional EvidenceStrongFunctional assays in patient fibroblasts demonstrated that loss of the chr14.232.a pseudogene product leads to decreased LRFN5 expression, which can be rescued by exogenous expression, indicating a direct mechanistic link (PMID:31152157). |