Article

Assignment of the Locus for PLO-SL, a Frontal-Lobe Dementia with Bone Cysts, to 19q13

Department of Human Molecular Genetics, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
The American Journal of Human Genetics (Impact Factor: 10.99). 02/1998; 62(2):362-72. DOI: 10.1086/301722
Source: PubMed

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.

0 Followers
 · 
122 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report the clinical case of a 43year old Italian woman and her family with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. PLOSL is a unique disease clinically characterized by a progressive presenile frontal-lobe dementia and multiple cystic bone lesions, typically leading to fractures of the limbs in the third decade of life. This rare recessively inherited disease is caused by mutations in one of two genes encoding different subunits of a receptor signalling complex, TYROBP and TREM2. In the present case fractures after microtrauma were not diagnosed, despite a radiological demonstration of the characteristic bone lesions in PLOSL. Further investigation led to the same diagnosis in her brother, with similar clinical presentation and the same mutation. Therefore a diagnosis of PLOSL should be considered in cases of presenile frontal-lobe dementia, even if the hallmark of pathological fractures is absent.
    Journal of the neurological sciences 03/2013; 326(1-2):115-9. DOI:10.1016/j.jns.2013.01.021 · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations.
    Skeletal Radiology 04/2014; 43(10). DOI:10.1007/s00256-014-1887-5 · 1.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary TLipo-membranous panniculitis or membrano-cystic steatonecrosis is an alteration of the adipose tissue. Sclerotic plaques with tendency to become chronic, do usually appear located on the lower area of the legs. It is almost exclusive in female mostly obese and diabetic and with a severe compo- nent of venous stasis. It has the histologic features of a lobule panniculitis, cystic cavities surrounded by fatty tissue with clear signs of steatonecrosis are formed by confluence. We present the case of a 36 years old female who developed a painful lesion on the location of a previous lesion, it had numerous nodule-cystic formations we noticed on palpation. The dermato-pathological study showed up the presence of cystic structures located on the lobules and at the level of the septum, surrounded by fatty tissue, with clear signs of steatonecrosis, a significant presence of frothy histiocytes and breakage of the cellular membranes with formation of micro-cysts. The cystic cavities were limited in their inner side by a serpiginous membrane, no nuclear, homogeneous and eosinophilic, PAS+, with a granulated appearance. It even formed in some areas pseudo-papillae, which projected them- selves towards the interior of the cyst. It has been suggested that ischemia is the main pathogenic cause for lipo-membranous panniculitis, although other reasons are also considered such as a previous trauma. Nowadays, we do not still know the reason why these changes are more prominent in certain patients than in other with the same disease.

Full-text

Download
45 Downloads
Available from
Jun 2, 2014