| 1. |
- Guo, Dongsheng, et al.
(författare)
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Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors
- 2006
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 111:3, s. 238-346
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Tidskriftsartikel (refereegranskat)abstract
- We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3–GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3–GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.
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| 2. |
- Holmlund, Camilla, 1969-, et al.
(författare)
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Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival.
- 2009
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Ingår i: Neuropathology (Kyoto. 1993). - : Wiley. - 0919-6544 .- 1440-1789. ; 29:3, s. 242-247
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Tidskriftsartikel (refereegranskat)abstract
- The three leucine-rich repeats and immunoglobulin-like domains (LRIG) genes encode integral membrane proteins. Of these, LRIG1 negatively regulates growth factor signaling and is implicated as a tumor suppressor in certain malignancies. In astrocytic tumors, the subcellular distribution of LRIG proteins is associated with specific clinicopathological features and patient survival. The role of LRIG proteins in oligodendroglioma has not previously been studied. Here we used immunohistochemistry to analyze the expression of the LRIG proteins in 63 oligodendroglial tumors, and evaluated possible associations between LRIG protein expression and clinicopathological parameters. Notably, cytoplasmic LRIG2 expression was found to be an independent prognostic factor associated with poor oligodendroglioma patient survival. This is the first report of an LRIG protein showing a negative effect on survival, suggesting that LRIG2 might have a function different from that of LRIG1, and possibly contributing to the etiology of oligodendroglioma.
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| 3. |
- Raheem, Olayinka, et al.
(författare)
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Hartia-lantiodystrofioiden molekyyligenetiikka Suomessa
- 2006
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Ingår i: Duodecim; lääketieteellinen aikakauskirja. - 0012-7183. ; 122:17, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Hartia-lantiolihasdystrofia (limb girdle muscular dystrophy, LGMD) oli ennen kyseisen taudin geenien löytämistä käytetty diagnoosi potilasryhmälle, jolla ei ole todettu muuta tunnistettua dystrofiaa, kuten X-kromosomaalista Duchennen tai Beckerin lihasdystrofiaa, vallitsevasti periytyvää fasioskapulohumeraalista lihasdystrofiaa, distaalista myopatiaa tai synnynnäistä lihasdystrofiaa. Suomessa tämän ryhmän potilailla on usein ollut diagnoosina dystrophia musculorum progressiva NUD. Vuonna 1991 löydettiin ensimmäinen LGMD:tä aiheuttava geenivirhe, ja nykyään voidaan molekyyligeneettisesti eritellä 17 eri alalajia, eivätkä nämäkään kata kaikkia tapauksia. Joidenkin alalajien diagnoosi on ollut mahdollista tehdä proteiinipuutoksen osoittavalla immunohistokemiallisella biopsialeikkeen värjäyksellä, ja menetelmä on tarjolla maamme neuropatologian laboratorioissa. TAYS:aan perustetussa lihastautien erityisdiagnostiikan keskuksessa on mahdollista etsiä tämän ryhmän geeni- ja proteiinivirheitä DNA- ja Western blotting -menetelmin. Mutaatiot kalpaiini 3-, FKRP- (fukutin-related protein) ja alfasarkoglykaanigeeneissä näyttävät olevan tärkeimmät suomalaisessa väestössä.
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| 4. |
- Tajsharghi, Homa, 1968, et al.
(författare)
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Human disease caused by loss of fast IIa myosin heavy chain due to recessive MYH2 mutations.
- 2010
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 133:Pt 5, s. 1451-9
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Tidskriftsartikel (refereegranskat)abstract
- Striated muscle myosin heavy chain is a molecular motor protein that converts chemical energy into mechanical force. It is a major determinant of the physiological properties of each of the three muscle fibre types that make up the skeletal muscles. Heterozygous dominant missense mutations in myosin heavy chain genes cause various types of cardiomyopathy and skeletal myopathy, but the effects of myosin heavy chain null mutations in humans have not previously been reported. We have identified the first patients lacking fast type 2A muscle fibres, caused by total absence of fast myosin heavy chain IIa protein due to truncating mutations of the corresponding gene MYH2. Five adult patients, two males and three females, from three unrelated families in UK and Finland were clinically assessed and muscle biopsy was performed in one patient from each family. MYH2 was sequenced and the expression of the corresponding transcripts and protein was analysed in muscle tissue. The patients had early-onset symptoms characterized by mild generalized muscle weakness, extraocular muscle involvement and relatively favourable prognosis. Muscle biopsy revealed myopathic changes including variability of fibre size, internalized nuclei, and increased interstitial connective and adipose tissue. No muscle fibres expressing type IIa myosin heavy chain were identified and the MYH2 transcripts were markedly reduced. All patients were compound heterozygous for truncating mutations in MYH2. The parents were unaffected, consistent with recessive mutations. Our findings show that null mutations in the fast myosin heavy chain IIa gene cause early onset myopathy and demonstrate that this isoform is necessary for normal muscle development and function. The relatively mild phenotype is interesting in relation to the more severe phenotypes generally seen in relation to recessive null mutations in sarcomeric proteins.
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| 5. |
- Tajsharghi, Homa, et al.
(författare)
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Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations
- 2014
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 22:6, s. 801-808
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Tidskriftsartikel (refereegranskat)abstract
- Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.
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