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PLXNB2 (HGNC:9104) has been implicated as a candidate gene in Phelan-McDermid syndrome (MONDO_0011652) based on multi‐patient studies that evaluated kidney anomalies in affected individuals. In a large registry encompassing 357 participants with Phelan-McDermid syndrome, kidney disorders such as renal dysplasia ([n = 19] PMID:37733098), vesicoureteral reflux, hydronephrosis, nephrolithiasis, polycystic kidney dysplasia, and general kidney abnormalities were reported. Moreover, an independent study of 10 patients with 22q13 terminal deletions further highlighted the potential role of PLXNB2 among other candidate genes in contributing to cerebellar and posterior fossa anomalies (PMID:23225497). Although these studies underscore a positional association through large-scale phenotypic analyses, clear segregation data or direct variant burden demonstrating PLXNB2 disruption in Phelan-McDermid syndrome remains limited.
At the molecular level, reported variants in PLXNB2, such as c.750C>A (p.Cys250Ter), have been identified in other contexts, yet their pathogenic effect specifically in Phelan-McDermid syndrome is not definitively established. Furthermore, functional experimental evidence directly linking PLXNB2 to the kidney or neurodevelopmental phenotypes observed in Phelan-McDermid syndrome is lacking. As a result, both the genetic and functional evidence are currently classified as Limited. Key take‑home: While preliminary multi‑patient data supports a role for PLXNB2 in the phenotypic spectrum of Phelan-McDermid syndrome, further segregation analyses and targeted functional studies are needed to confirm its clinical utility in diagnostic and therapeutic decision‑making.
Gene–Disease AssociationLimitedPositional mapping from a registry of 357 participants and imaging data from 10 subjects support an association, but direct segregation and variant-specific evidence are lacking (PMID:37733098, PMID:23225497). Genetic EvidenceLimitedCandidate gene status is inferred from multi-patient studies describing kidney anomalies in Phelan-McDermid syndrome, without clear segregation of PLXNB2 variants. Functional EvidenceLimitedNo direct functional assays have been reported that link PLXNB2 disruption to the kidney or neurodevelopmental phenotypes observed in Phelan-McDermid syndrome. |