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. 1998 Feb;62(2):362–372. doi: 10.1086/301722

Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13.

P Pekkarinen 1, I Hovatta 1, P Hakola 1, O Järvi 1, M Kestilä 1, U Lenkkeri 1, R Adolfsson 1, G Holmgren 1, P O Nylander 1, L Tranebjaerg 1, J D Terwilliger 1, J Lönnqvist 1, L Peltonen 1
PMCID: PMC1376898  PMID: 9463329

Abstract

PLO-SL (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile frontal-lobe dementia, resulting in death at <50 years of age. Since the 1960s, approximately 160 cases have been reported, mainly in Japan and Finland. The pathogenesis of the disease is unknown. In this article, we report the assignment of the locus for PLO-SL, by random genome screening using a modification of the haplotype-sharing method, in patients from a genetically isolated population. By screening five patient samples from 2 Finnish families, followed by linkage analysis of 12 Finnish families, 3 Swedish families, and 1 Norwegian family, we were able to assign the PLO-SL locus to a 9-cM interval between markers D19S191 and D19S420 on chromosome 19q13. The critical region was further restricted, to approximately 1.8 Mb, by linkage-disequilibrium analysis of the Finnish families. According to the haplotype analysis, one Swedish and one Norwegian PLO-SL family are not linked to the chromosome 19 locus, suggesting that PLO-SL is a heterogeneous disease. In this chromosomal region, one potential candidate gene for PLO-SL, the gene encoding amyloid precursor-like protein 1, was analyzed, but no mutations were detected in the coding region.

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Selected References

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