Benutzerspezifische Werkzeuge

Molekulare Endokrinologie und neuromuskuläre Erkrankungen, Neuropädiatrie

Leiterin

Prof. Dr. med. Angela HübnerProf. Dr. med. Angela Hübner (Foto)

Mitarbeiter:

Dr. rer. nat. Katrin Köhler (Postdoktorandin, Biochemikerin)
Prof. Dr. med. Maja von der Hagen (Leiterin der Abt. Neuropädiatrie)
Dr. med. Jan Idkowiak (Assistenzarzt, z.Zt. Forschungsstipendium in UK)
Dipl.-Biol. Sebastian Gärtner
Ramona Jühlen, Master of Science
Dana Landgraf (MTA)

Forschungsprojekte

  • Klinische und genetische Untersuchungen zu verschiedenen Formen des ACTH-Resistenz-Syndroms
  • Untersuchungen zur zellulären Funktion des Nukleoporins ALADIN und zu seiner Rolle bei der Pathogenese des Triple-A-Syndroms (DFG-Förderung)
  • Mechanisms of adrenal dysregulation in triple A syndrome (DFG-Klinische Forschergruppe KFO252, Teilprojekt 6)
  • Genotyp-Phänotyp-Analysen neuromuskulärer Erkrankungen im Kindes- und Jugendalter

Doktoranden (Dr. med.):

  • Daniela Klaus „Genotyp-Phänotyp-Vergleich beim Triple-A-Syndrom“
  • Stephanie Meyer „Untersuchung synthetischer ALADIN-Mutanten der Proteinregion L430F“
  • Marie-Christin Modler „Phänotypische Charakterisierung eines Knock-In-Mausmodells für das Triple-A-Syndrom“
  • Friederike Walter „Nachuntersuchungen von Patienten mit hypogonadotropem oder hypergonadotropem Hypogonadismus“
  • Hendrick Drechsel “Ergebnisse der Nachuntersuchung ehemaliger Patienten mit hypophysärer Insuffizienz am Universitätsklinikum Dresden“

Publikationen:

ACTH-Resistenz-Syndrome

Handschug K, Sperling S, Yoon, SJK, Hennig, S, Clark, AJL, Huebner A. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet 2001;10:283-290.

Krumbholz M, Koehler K, Huebner A. Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome. Biochem Cell Biol 2006;84:243-249.

Huebner A, Mann P, Rhode E, Kaindl AM, Witt M, Verkade P, Jakubicka S, Menschikowski M, Stoltenburg-Didinger G, Koehler K. Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome. Mol Cell Biol 2006;26:1879-1887.

Koehler K, Brockmann K, Krumbholz M, Kind B, Bonnemann, C, Gärtner J, Huebner A. Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe. Eur J Hum Genet 2008; 16:1499-1506.

Storr HL, Kind B, Parfitt DA, Chapple JP, Lorenz, Koehler K, Huebner A, Clark AJL. Deficiency of nuclear ferritin heavy chain nuclear import in Triple A syndrome implies nuclear oxidative damage as the primary disease mechanism. Mol Endocrinol 2009;23:2086-2094.

Kind B, Koehler K, Huebner A. The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. Biochem Biophys Res Co 2009;390:205-210.

Ferraz-de Souza B, Martin F, Mallet D, Hudson-Davies R, Cogram P, Lin L, Gerrelli D, Beuschlein F, Morel Y, Huebner A, Achermann JC. CBP/p300-interacting transcativator, with Glu/Asp-rich C-terminal domain 2, and pre-B-cell –leukemia transcription factor 1 in human adrenal development and disease. J Clin Endocr Metab 2009;94:678-683.

Metherell L, Naville D, Halaby G, Begeot M, Huebner A, Nürnberg G, Nürnberg P, Green J, Tomlinson JW, Krone NP, Lin L, Racine M, Berney DM, Achermann JC, Arlt W, Clark AJL. Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency. J Clin Endocr Metab 2009;94:3865-3871.

Palka C, Giuliani R, Brancati F, Mohn A, Di Muzio A, Huebner A, De Grandis D, Chiarelli F, Ferlini A, Stoppia, L. Two Italian patients with novel AAAS gene mutation expand allelic and phenotypic spectrum of triple A (Allgrove) syndrome. Clin Genet 2010;77:298-301.

Kind B, Koehler K, Krumbholz M, Landgraf D, Huebner A. Intracellular ROS level is increased in fibroblasts of triple A syndrome patients. J Mol Med 2010;88:1233-42.

Milenkovic T, Zdravkovic D, Savic N, Todorovic S, Mitrovic K, Koehler K, Huebner A. Triple A syndrome: 32 years experience of a single centre (1977-2008). Eur J Pediatr. 2010;169:1323-8.

Krull I, M-Woelfle M, Bärlocher K, Koehler K, Huebner A, Brändle M. Two patients with an identical novel mutation in the AAAS gene and similar phenotype of triple A (Allgrove) syndrome. Exp Clin Endocrinol Diabetes. 2010;118:530-6.

Moschos MM, Margetis I, Koehler K, Gatzioufas Z, Huebner A. New ophthalmic features in a family with triple A syndrome. Int Ophthalmol. 2011;31:239-43.

Dumić M, Barišić N, Rojnić-Putarek N, Kušec V, Stanimirović A, Koehler K, Huebner A. Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy. Eur J Pediatr. 2011;170:393-6.

Dumic M, Barišic N, Kusec V, Stingl K, Skegro M, Stanimirovic A, Koehler K, Huebner A. Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. Eur J Pediatr. 2012;171:1453-9.

Koehler K, End K, Kind B, Landgraf D, Mitzscherling P, Huebner A. Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress. Horm Metab Res. 2012 accepted

Neuromuskuläre Erkrankungen

Kaindl AM, Rüschendorf F, Krause S, Goebel HH, Koehler K, Becker C, Pongratz D, Müller-Höcker J, Nürnberg P, Stoltenburg-Didinger G, Lochmüller H, Huebner A. Missense mutations of ACTA1 cause dominant congenital myopathy with cores. J Med Genet 2004;41:842-848.

Kaindl AM, Jakubiczka S, Luecke T, Bartsch O, Weis J, Stoltenburg-Didinger G, Aksu F, Oexle K, Koehler K, Huebner A. A homozygous microdeletion of chromosome 4q11-12 causes severe limb-girdle muscular dystrophy type 2E with joint hyperlaxity and contractures. Hum Mutat 2005;26:279-280.

Vorgerd M, van der Ven PFM, Bruchertseifer V, Löwe T, Kley RA, Schröder R, Lochmüller H, Himmel M, Koehler K, Fürst DO, Huebner A. A mutation in the dimerization domain of filamin c causes a novel type of autosomal-dominant myofibrillar myopathy. Am J Hum Genet 2005;77:297-304.

von der Hagen M, Kaindl AM, Köhler K, Mitzscherling P, Häusler HJ, Stoltenburg-Didinger G, Huebner A. Limb girdle muscular dystrophy type 2I caused by a novel missense mutation in the FKRP gene presenting as acute virus-associaed myositis in infancy. Eur J Pediatr 2006;165:62-63.

von der Hagen M, Schallner J, Kaindl AM, Abicht A, Müller J, Korinthenberg R, Kress, Walter MC, von Moers A, Mitzscherling P, Korinthenberg R, Schara U, Müller J, Grieben U, Koehler K, Müller-Reible C, Hübner C, Lochmüller H, Huebner A. Facing the genetic heterogeneity in neuromuscular disorders: linkage-analyses as economic diagnostic approach towards the molecular diagnosis. Neuromuscular Disord 2006;16:4-13.

von der Hagen M, Kress W, Hahn G, Brocke KS, Mitzscherling P, Huebner A, Müller-Reible C, Stoltenburg-Didinger G, Kaindl AM. Novel RYR1 missense mutation causes core rod myopathy. Eur J Neurol 2008;15:e31-e32.

Fischer D, Kley R, Strach K, Meyer C, Sommer T, Eger K, Rolfs A, Meyer W, Pou A, Pradas J, Heyer CM, Grossmann A, Huebner A, Kress W, Reimann J, Schröder R, Eymard B, Fardeau M, Udd B, Goldfarb L, Vorgerd M, Olivé M. Distinct muscle imaging patterns in myofibrillar myopathies. Neurology 2008;71:758-765.

Borg K, Stucka R, Locke M, Melin E, Ahlberg G, Klutzny U, von der Hagen M, Huebner A, Lochmüller H, Wrogemann K, Thornell LE, Blake DJ, Schoser B. Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H. Hum Mutat 2009;30:E831-844.

Goebel HH, Bönnemann CG, Rare Structural Myopathy Consortium. Workshop Report, 169th ENMC International Workshop Rare Structural Congenital Myopathies, 6-8- Novemer 2009, Naarden, The Netherlends. Neuromuscular Disord. 2011;21:363-374.

Mihaylova V, Salih MA, Mukhtar MM, Abuzeid HA, El-Sadig SM, von der Hagen M, Huebner A, Nürnberg G, Abicht A, Müller JS, Lochmüller H, Guergueltcheva V. Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. Neurology. 2009;73:1926-8.

Mihaylova V, Scola RH, Gervini B, Lorenzoni PJ, Kay CK, Werneck LC, Stucka R, Guergueltcheva V, von der Hagen M, Huebner A, Abicht A, Müller JS, Lochmüller H. Molecular characterisation of congenital myasthenic syndromes in Southern Brazil. J Neurol Neurosurg Psychiatry. 2010;81(9):973-7.

Kottlors M, Moske-Eick O, Huebner A, Krause S, Müller K, Kress W, Schwarzwald, R, Bornemann A, Haug V, Kirschner J. Late-onset autosomal dominant limb girdle muscular dystrophy and Paget’s disease of bone unlinked to the VCP gene locus. J Neurol Sci 2010 ;291 :79-85.

Kirschner J, Schessl J, Schara U, Reitter B, Stettner GM, Hobbiebrunken E, Wilichowski E, Bernert G, Weiss S, Stehling F, Wiegand G, Müller-Felber W, Thiele S, Grieben U, von der Hagen M, Lütschg J, Schmoor C, Ihorst G, Korinthenberg R. Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial. Lancet Neurol. 2010;9:1053-9.

Senderek J, Müller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hübner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmüller H. Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am J Hum Genet. 2011;88:162-72.

Hicks D, Sarkozy A, Muelas N, Koehler K, Huebner A, Hudson G, Chinnery PF, Barresi R, Eagle M, Polvikoski T, Bailey G, Miller J, Radunovic A, Hughes PJ, Roberts R, Krause S, Walter MC, Laval SH, Straub V, Lochmüller H, Bushby K. A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy. Brain. 2011;134:171-82.

Lehtokari VL, Pelin K, Herczegfalvi A, Karcagi V, Pouget J, Franques J, Pellissier JF, Figarella-Branger D, von der Hagen M, Huebner A, Schoser B, Lochmüller H, Wallgren-Pettersson C. Nemaline myopathy caused by mutations in the nebulin gene may present as a distal myopathy. Neuromuscul Disord. 2011;21:556-62.

Rohayem J, Ehlers C, Wiedemann B, Holl R, Oexle K, Kordonouri O, Salzano G, Burger W, Meissner T, Schober E, Huebner A, Lee-Kirsch MA. Diabetes mellitus and neurodegeneration in Wolfram syndrome: a multicenter study of phenotype and genotype. Diabetes Care 2011;34:1503-1510.

Michot C, Hubert L, Romero NB, Gouda A, Mamoune A, Mathew S, Kirk E, Viollet L, Rahman S, Bekri S, Peters H, McGill J, Glamuzina E, Farrar M, von der Hagen M, Alexander IE, Kirmse B, Barth M, Laforet P, Benlian P, Munnich A, Jeanpierre M, Elpeleg O, Pines O, Delahodde A, de Keyzer Y, de Lonlay P. Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia. J Inherit Metab Dis. 2012;35:1119-28.

Abicht A, Dusl M, Gallenmüller C, Guergueltcheva V, Schara U, Della Marina A, Wibbeler E, Almaras S, Mihaylova V, von der Hagen M, Huebner A, Chaouch A, Müller JS, Lochmüller H. Congenital myasthenic syndromes: achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: a study of 680 patients. Hum Mutat. 2012;33:1474-84.

Di Donato N, Riess A, Hackmann K, Rump A, Huebner A, von der Hagen M, Hahn G, Schrock E, Tinschert S. Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: Alternative definition and further delineation of MOMO syndrome. Am J Med Genet A. 2012;158A:2857-62.

Hackmann K, Matko S, Gerlach EM, von der Hagen M, Klink B, Schrock E, Rump A, Di Donato N. Partial deletion of GLRB and GRIA2 in a patient with intellectual disability. Eur J Hum Genet. 2012. doi: 10.1038/ejhg.2012.97.

Davidson AE, Siddique FM, Lopez MA Lunt P, Carlson HA, Moore BE, Love S, Born DE, Roper H, Majumdar A, Jayadev S, Underhill HR, von der Hagen M, Huebner A, Jardine P, Merrison A, Curtis E, Cullup T, Jungbluth H, Cox MO, Winder TL, Abdelsalam H, Li JZ, Moore SA, Dowling JJ. Novel deletion of lysine 7 expands the clinical, histopathologic and genetic spectrum of TPM2-related myopathies. Brain 2012, accepted

Kooperationen

Prof. Dr. A.J.L.Clark (St. Bartholomew’s Hospital London, UK)
Ph.D. Eric Griffis Lab (University of Dundee – College of Life Sciences, UK)
Prof. Wiebke Arlt (Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham)

Links

http://www.md-net.org/servicestrukturen/mikrosatellitenanalyse/
http://www.kfo252.de/