Espeel, Marc

Eyskens, François

Giros, Marisa

Gootjes, Jeannette

Mandel, Hanna

Pineda, Mercedes

Poll-The, Bwee Tien

Roels, Frank

Saudubray, Jean-Marie

English

Ghent University Academic Bibliography

NVvM, Papendal, 11 dec 2003Peroxisomal mosaics in patients :modulation of gene expression ?Frank RoelsPathologie, Universiteit GentAGTDABDABHuman peroxisomal disordersPxbiogenesis=assemblydeficiencies*Zellweger= CHRs*NeonatalALD/ 50 000*InfantileRefsumdisease*Mosaics10/170Single enzym/protein deficiencies°X-ALD=ALDprot mut; funct defof VLCacyl-CoA synthase/ 35 000°Acyl-CoA oxidase deficiency°D-bifunctional enzyme defic.°(Thiolase (straight chain) def.)°Racemase deficiency°RCDP 2=DHAPAT defic.°RCDP3=alkylDHAP synthase def.°Classical=adult Refsum dis =phytanoylCoA hydroxylase def.°Mevalonate kinase def.°Isolated hyperpipecolic acidemia°Primary hyperoxaluria1=AGT def°Mulibrey nanism=TRIM37 defic.MultipleenzymedeficienciesRhizomelicchondro-dysplasiapunctatatype 1Clinical and biochemical datamildmosaicnornor20%norplasmal25%50%nornorCultur.fibrobl2y:eye,mental12y!neuro-degen,eyecontactPneumoniasyntaxvocabschool8ycataractPMRdeafmenarchewalks,talkspyr treyecontactneurodegen,vegetEvolutnonono±+nono±±nodysmornornornornornornorNeonatnornornornor↓mild↓nornorPlasmalnor↑↑↑↑↑↑↑Phyt++++++++Bile ac↑↑↑↑↑↑↑↑↑↑VLCFA43y†24y14y†13 m7y† 17y†15y11y†8y7†13y6AgePt10Pt9Pt 8Pt 7Pt 6Pt 5Pt 4Pt3Pt 2Pt 1thiolase43 kDa PMPAGTPolarized lightAcid phosphataseAcid phosphatase (cerium)15y : cerebellum, PAS, polaracylCoA oxidaseacylCoA oxidaseAGTthiolase; no catalase & AGTHow can peroxisome mosaics be explained ?a) genome is different:somatic mutation?  but consanguinous parents, 2brothers.⇒ DNA analysis of + and - areas (LCM).b) same mutations but differentiallyexpressed:Human peroxisome biogenesis genesNALDZSZSNALDZS,NALD,IRDZS,NALDRCDP 1ZS,NALDZS,NALDZSZSZS,NALD,IRDPhenotypePEX 26PEX 19PEX 16PEX 13PEX 12PEX 10PEX 7PEX 6PEX 5PEX 3PEX 2PEX 1GeneCG8CG14CG9CG13CG3CG7CG11CG4 & 6CG2CG12CG10CG1ComplGrPMP34PMP receptorPMPSH3,PMPRING, PMPRING, PMPPTS2 receptorAAA ATPasePTS1 receptorPMPRING, PMP35AAA ATPaseProteinJutta GärtnerPex6p(mut) is compensated byoverexpession of Pex1p (Geisbrecht et al,1998)                         interacts with Pex26p (Matsumoto et al, 2003) is temperature sensitive (Imamuraet al, 2000)Pex2p(mut) is compensated byoverexpression of PMP70 (Gärtner et al,1998);is temperature sensitive (akiyama et al, 2002)⇒Pexprotein interrelationships &modulation :Function of mutated gene productPex6p can  be modulated by theamount≈activity of Pexp1 and Pex26pand temperature;and of mut Pex2p by theamount≈activity of PMP70 andtemperature.Since (most) protein concentrationsnormally vary between hepatocytes, for exalbumin,Hypothesis to explainmosaic:Normal peroxisome biogenesis isrestored in cells wherecompensatory proteins are high(pex1p, Pex26p, PMP70); and whentemperature is low.AcknowledgementsThe parentsHanna Mandel, HaifaMarisa Giros, BarcelonaFrançois Eyskens, AntwerpenMercedes Pineda, BarcelonaJose Prats, BaracaldoBwee Tien Poll-The, Jeannette Gootjes &Ronald Wanders, AmsterdamNieves Saracibar & Begoña A. Pueyo, VitoriaJean-Marie Saudubray, ParisRefs:Marianne Depreter et al: Humanperoxisomal disorders, 2003, MicroscRes Techn 61: 203-223“Peroxisomal disorders and regulationof genes”, eds Roels, Baes, DeBie, 416pp., Kluwer Acad Publ, in press.

Peroxisome mosaics in patients : modulation of gene expression?

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Peroxisome mosaics in patients : modulation of gene expression?

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