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In the two published case reports (PMID:20635403), patients with 22q13.3 deletion syndrome presented with severe developmental delay, absent speech, and fulminant hepatic failure requiring liver transplantation. These studies identified large terminal deletions that encompass approximately 39–55 genes, with PIM3 highlighted as a prime candidate for contributing to the hepatic failure phenotype. The evidence is based on these isolated case observations with no additional segregation data and no accompanying functional assays specific to PIM3, thereby limiting the overall genetic support for a direct gene–disease relationship.
The limited genetic evidence suggests that while the deletion indicates a potential role for PIM3 in the phenotype, the absence of targeted functional studies precludes a stronger assertion. Nonetheless, the report recommends that liver function tests and array‐CGH should be considered in patients with Phelan‑McDermid syndrome to help identify those at risk for developing fulminant hepatic failure. Key take‑home: Even preliminary associations, such as that of PIM3 with liver failure in this syndrome, can inform clinical surveillance and management decisions.
Gene–Disease AssociationLimitedAssociation based on two independent case reports (PMID:20635403) involving large terminal deletions that implicate PIM3 as a candidate gene for fulminant hepatic failure. Genetic EvidenceLimitedThe genetic evidence is derived solely from deletion cases with no specific coding variants reported and lacking segregation data, thus only modestly supporting the gene–disease relationship. Functional EvidenceLimitedNo direct functional studies or experimental assessments were provided to clarify the pathogenic mechanism of PIM3 in this context. |