Boltshauser
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Neuropädiatrie, Abteilung » Prof. Dr. Eugen Boltshauser (emeritiert) » Boltshauser
Completed research project
| Title / Titel | Genetic cerebellar malformations: definition / delineation / outcome / molecular genetics | ||||
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| Abstract (PDF, 14 KB) | |||||
| Original title / Originaltitel | Genetisch bedingte zerebelläre Missbildungssyndrome: Definition / Molekulargenetik / Langzeitverlauf | ||||
| Summary / Zusammenfassung | For a number of cerebellar malformations the exact delineation to other overlapping syndromes is still debatable, this applies in particular to Joubert syndrome, an autosomal recessive condition characterised by vermis aplasia, and other neuroimaging abnormalities, and clinically characterised by mental retardation, ataxia and ocular movement abnormalities. It is not yet clear whether patients with retinal and/or renal involvement have a subtype of Joubert syndrome or belong to a different category. So far at our hospital we have contributed several publications to this topic and we are engaged in further follow-up and delineation of these syndromes. In particular we collaborate with other colleagues regarding molecular genetics of Joubert syndrome, which is definitely heterogeneous.Up to now 10 genes have been identified in association with Joubert and related disorders. There is an expanding number of syndromes with molar tooth malformation on MRI, which we are studying(including Meckel,OFD VI). Along the same line we are following other more or less defined cerebellar syndromes, describing neuroimaging and outcome(such as rhombencephalosynapsis, pontocerebellar hypoplasia type 2, Gomez-Lopez-Hernandez syndrome, pontine tegmental cap dysplasia) Retrospective analysis of neuroimaging data of a large series of patients with Joubert Syndrome and Related Disorders has allowed to provide the spectrum of infra- and supratentorial findings in JSRD, and the recognition of a new MR finding, namely interpeduncular heterotopia. |
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| Publications / Publikationen | Lagier-Tourenne C, Boltshauser E, Breivik N et al. Homozygosity mapping of a third Joubert syndrome locus to 6q23. J Med Genet 2004;41:273-277ValenteEM,Marsh SE,Castori M,Dixon-Salazar T,Bertini E,Al-Gazali L,Messer J,Barbot C,Woods CG,Boltshauser E, et al:Distinguishing the four genetic causes of Joubert syndrome-related disroders.Ann Neurol 2005;57:513-519Valente EM,Brancati F,Silhavy JL,Castori M,Marsh SE,Barrano G,Bertini E,Boltshauser E, et al: AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.Ann Neurol 2006;59:527-534Valente EM, Silhavy JL, Brancati F, ...Boltshauser E,...Gleeson JG:Mutaions in CEP 290, which encoedes a centrosomal protein, cause pleiotropic forms of Joubert syndrome.Nat Genet 2006;38:623-625Steinlin M, Klein A, Haas-Lude K, Zafeiriou D, Strozzi S, Mueller T, Gubser-Mercati D, Schmitt Mechelke T, Kraegeloh-Mann I, Boltshauser E: Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings. Eur J Paed Neurol 2007,11:146-152 epub DOI:10.1016/j.ejpn.200611.012Poretti A, Boltshauser E, Plecko B: Brainstem disconnection: case report and review of the literature. Neuropediatrics 2007;38:210-212Poretti A, Brehmer U, Scheer I, Bernet V, Boltshauser E: Prenatal and neonatal MR imaging in oral-facial-digital syndrome type VI. AJNR 2008;29:1090-1Brancati F, Travaglini, Zablocka D, Boltshauser E, et al:RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders. Clin Genet 2008;74:164-70Brancati F,...Boltshauser E,....Valente EN: MKS3/TMEM67 mutations are a major cause of COACH syndrome, a Joubert syndrome related disorder with liver involvement. Human Mutation, 2009;30(2):E32-42Rauscher C, Poretti A, Neuhann TM, Forstner R, Hahn G, Koch J, Tinschert S, Boltshauser E: Pontine tegmental cap dysplasia: the severe end of the spectrum. Neuropediatrics 2009;40:43-46Sturm, V, Leiba H, Menke MN, Valente EM, Poretti A, Landua K, Boltshauser E: Ophthalmological findings in Joubert syndrome. Eye 2010;24:222-5,epub May 22,2009Bielas SL, Silhavy JL....Boltshauser E, Valente EM, Gleeson JG: Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol siganling to the ciliopathies. Nat Genet 2009;41:1032-36Valente EM, Logan CV,...Boltshauser E,...Attie-Bitach T, Gleeson JG: Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 2010;42:619-25Poretti A, Huisman TA. Scheer I, Boltshauser E: Joubert syndrome and related disorders:spectrum of neuroimaging findings in 75 patients. A Am J Neuroradiol AJNR 2011;32:1459-63Harting I, Kotzaeridou U, Poretti A, Seitz A, Pietz J, Bendszus M. Boltshauser E: Interpeduncular heterotopie in Joubert syndrome: a previously undescribed MR finding. Am J Neuroradiol AJNR 2011;32:1286-89Dafinger C, Liebau M, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke G, Fabretti F,...Bolz HJ: Mutations in KIF7 link Joubert syndrome with sonic hedgehog signaling and microtubule dynamics. J Clin Invest 2011;121:2662-67Poretti A, Vitiello G, Hennekam RCM, Arrigoni F, Bertini E.......Valente EM, Boltshauser E: Delineation and diagnostic criteria of oral-facial-digital syndrome type VI. Orphanet J Rare Dis 2012,7:4 | ||||
| Keywords / Suchbegriffe | Joubert syndrome, molar tooth malformation, rhombencephalosynapsis,oro-facio-digital syndrome type VI,pontocerebellar hypoplasia, Gomez-Lopez-Hernandez syndrome | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Others No funding. |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Sep 1999 to Jan 2012 |