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This report evaluates the association of APLP1 with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL), a recessively inherited disorder characterized by systemic bone cysts and a presenile frontal‐lobe dementia leading to death before the age of 50 (PMID:9463329, PMID:9828133). Multiple studies involving linkage analysis in genetically isolated populations from Finland, Sweden, and Norway (aggregating data from approximately 18 families and ~160 reported cases) have mapped the PLO-SL locus to a 9-cM interval on chromosome 19q13. In these studies, APLP1 emerged as a positional candidate gene under an autosomal recessive inheritance model.
Despite the robust segregation and linkage findings, comprehensive mutation screening of the coding region of APLP1 did not identify any pathogenic variants. In the absence of confirmed genetic alterations or supporting functional assays that demonstrate a deleterious effect on protein function, the evidence for a direct causal role of APLP1 in PLO-SL remains limited. This emphasizes the need for further molecular and experimental analyses to resolve the gene’s contribution, while the current linkage data nonetheless provides useful information for clinical diagnostic decision-making.
Gene–Disease AssociationLimitedDespite linkage evidence in 18 families and ~160 reported cases (PMID:9463329, PMID:9828133), no pathogenic coding variants in APLP1 were identified. Genetic EvidenceLimitedMultiple families demonstrated autosomal recessive segregation with shared haplotypes; however, mutation screening revealed no coding variants to support a causative role for APLP1 in PLO-SL. Functional EvidenceLimitedNo functional assays directly linking APLP1 to the PLO-SL phenotype were reported, leaving the mechanistic basis for its involvement unconfirmed. |