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Faculty Detail    
Name LUDWINE M MESSIAEN
  
Campus Address KAUL 330 Zip 0021
Phone  (205) 996-2915
E-mail  lmessiae@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Clinical Genetics  Clinical Genetics Professor Adjunct

Graduate Biomedical Sciences Affiliations
Genetics, Genomics and Bioinformatics 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 
Neuroscience Graduate Program 

Biographical Sketch 
Dr. Messiaen is a graduate of the Institute for Psychosocial Education in Kortrijk, Belgium. She completed her MS and PhD degrees (Molecular biology and cancer) at the University of Ghent in Flanders, Belgium, and then joined the staff of the Center of Medical Genetics at Ghent University Hospital, where she directed the molecular diagnostic laboratory from 1991 to 2003. She joined UAB in summer 2003 where she directs the Medical Genomics Laboratory in the Department of Genetics.

Society Memberships
Organization Name Position Held Org Link
American College of Medical Genetics  FACMG   
Human Genome Variation Society   member   
European Society of Human Genetics  member   
American Society of Human Genetics  member   
 



Research/Clinical Interest
Title
Molecular genetics testing in hereditary disorders; molecular dissection of the variant forms of NF1
Description
My research is focused on the development and provision of comprehensive genetic tests for a number of rare and common genetic disorders. My laboratory currently offers molecular diagnostic testing for all forms of neurofibromatoses (NF1, NF2, schwannomatosis, spinal NF, NF-Noonan, segmental or mosaic NF), Legius syndrome, Tuberous Sclerosis, the ras-o-pathies, Von Hippel-Lindau disorder, PTEN—disorder, autosomal recessive polycystic kidney disease, and others. My research has a special focus on Neurofibromatosis type1 and phenotypically overlapping disorders including Legius syndrome. We are interested to fully explore the diverse spectrum of NF1 mutations. We explore NF1 genotype-phenotype correlations using several complementary approaches, including comparison of discrete phenotypic signs in unrelated patients carrying an identical NF1 mutation, characterization of cells/tissues affected in patients with mosaic or segmental NF, definition of the mutational spectrum in patients with variant forms of NF (spinal NF, Watson syndrome, NF-Noonan).

Selected Publications 
Publication PUBMEDID
Hsiao MC, Piotrowski A, Callens T, Fu C, Wimmer K, Claes KB, Messiaen L. (2015) Decoding NF1 Intragenic Copy-Number Variations. Am J Hum Genet.;97(2):238-49.   26189818 
Rojnueangnit K, Xie J, Gomes A, Sharp A, Callens T, Chen Y, Liu Y, Cochran M, Abbott MA, Atkin J, Babovic-Vuksanovic D, Barnett CP, Crenshaw M, Bartholomew DW, Basel L, Bellus G, Ben-Shachar S, Bialer MG, Bick D, Blumberg B, Cortes F, David KL, Destree A, Duat-Rodriguez A, Earl D, Escobar L, Eswara M, Ezquieta B, Frayling IM, Frydman M, Gardner K, Gripp KW, Hernández-Chico C, Heyrman K, Ibrahim J, Janssens S, Keena BA, Llano-Rivas I, Leppig K, McDonald M, Misra VK, Mulbury J, Narayanan V, Orenstein N, Galvin-Parton P, Pedro H, Pivnick EK, Powell CM, Randolph L, Raskin S, Rosell J, Rubin K, Seashore M, Schaaf CP, Scheuerle A, Schultz M, Schorry E, Schnur R, Siqveland E, Tkachuk A, Tonsgard J, Upadhyaya M, Verma IC, Wallace S, Williams C, Zackai E, Zonana J, Lazaro C, Claes K, Korf B, Martin Y, Legius E, Messiaen L. High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation. Hum Mutat. 2015 Jul 14. doi: 10.1002/humu.22832. [Epub ahead of print]  26178382 
Kehrer-Sawatzki H, Bengesser K, Callens T, Mikhail F, Fu C, Hillmer M, Walker ME, Saal HM, Lacassie Y, Cooper DN, Messiaen L. Identification of large NF1 duplications reciprocal to NAHR-mediated type-1 NF1 deletions. Hum Mutat. 2014: 35(12): 1469-75.  25205021 
Piotrowski A, Xie J, Liu YF, Poplawski AB, Gomes AR, Madanecki P, Fu C, Crowley MR, Crossman DK, Armstrong L, Babovic-Vuksanovic D, Bergner A, Blakeley JO, Blumenthal AL, Daniels MS, Feit H, Gardner K, Hurst S, Kobelka C, Lee C, Nagy R, Rauen KA, Slopis JM, Suwannarat P, Westman JA, Zanko A, Korf BR, Messiaen LM. (2014) Germline Loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat. Genet. 46(2): 182-187  24362817 
Stewart DR, Brems H, Gomes AG, Ruppert SL, Callens T, Williams J, Claes K, Bober MB, Hachen R, Kaban LB, Li H, Lin A, McDonald M, Melancon S, Ortenberg J, Radtke HB, Samson I, Saul RA, Shen J, Siqveland E, Toler TL, van Maarle M, Wallace M, Williams M, Legius E, Messiaen L. Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations or a distinct disorder. 2014:Genet. Med. 16(6): 448-459  24232412 
Brems, H., Pasmant, E., Van Minkelen, R., Wimmer, K., Upadhyaya, M., Legius, E., Messiaen, L. (2013) Review and update of SPRED1 mutations causing Legius syndrome. Hum. Mutat. 33(11): 1538-46  22753041 
Kannu, P., Nour, M., Irving, M., Xie, J., Loder, D., Lai, J., Islam, O., MacKenzie, J., Messiaen, L. Paraspinal ganglioneuroma in the proband of a large family with mild cutaneous manifestations of NF1, carrying a deep NF1 intronic mutation. Clin. Genet. 2013;83(2): 191-4  22533502 
Wimmer, K., Callens, T., Wernstedt, A., Messiaen, L. The NF1 gene contains hotspots for L1 endonuclease-dependent de novo insertion. PLoS Genet 2011;7(11)  22125493 
Messiaen, L., Vogt, J., Bengesser, K., Fu, C., Mikhail, F., Serra, E., Garcia-Linares, C., Cooper, D.N., Lazaro, C., Kehrer-Sawatzki, H. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1) Hum Mutat. 2011;32(2):213-9  21280148 
Spencer E, Davis J, Mikhail F, Fu C, Vijzelaar R, Zackai EH, Feret H, Meyn MS, Shugar A, Bellus G, Kocsis K, Kivirikko S, Poyhonen M, Messiaen L. Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR. Am. J. Med. Genet. A 2011, 155(6): 1352-1359.  21548021 
Jouhilahti EM, Peltonen S, Callens T, Jokinen E, Heape AM, Messiaen L, Peltonen J. The devlopment of cutaneous neurofibromas. Am. J. Pathol. 2011: 178(2):500-5  21281783 
Messiaen L, Vogt J, Bengesser K, Fu C, Mikhail F, Serra E, Garcia-Linares C, Cooper DN, Lazaro C, Kehrer-Sawatzki H. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1). Hum Mutat. 2010 Nov 30
 		 21120953 
Hölzel M, Huang S, Koster J, Ora I, Lakeman A, Caron H, Nijkamp W, Xie J, Callens T, Asgharzadeh S, Seeger RC, Messiaen L, Versteeg R, Bernards R. NF1 is a tumor suppressor in neuroblastoma that determines retinoic acid response and disease outcome. Cell. 2010 Jul 23;142(2):218-29.

 		 20655465 
Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E. Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. JAMA. 2009 Nov 18;302(19):2111-8.
 		 19920235 
Brems H, Park C, Maertens O, Pemov A, Messiaen L, Upadhyaya M, Claes K, Beert E, Peeters K, Mautner V, Sloan JL, Yao L, Lee CC, Sciot R, De Smet L, Legius E, Stewart DR. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res. 2009 Sep 15;69(18):7393-401
 		 19738042 
McGillicuddy LT, Fromm JA, Hollstein PE, Kubek S, Beroukhim R, De Raedt T, Johnson BW, Williams SM, Nghiemphu P, Liau LM, Cloughesy TF, Mischel PS, Parret A, Seiler J, Moldenhauer G, Scheffzek K, Stemmer-Rachamimov AO, Sawyers CL, Brennan C, Messiaen L, Mellinghoff IK, Cichowski K. Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis. Cancer Cell. 2009 Jul 7;16(1):44-54.

 		 19573811 
De Schepper S, Maertens O, Callens T, Naeyaert JM, Lambert J, Messiaen L. Somatic mutation analysis in NF1 café au lait spots reveals two NF1 hits in the melanocytes. J Invest Dermatol. 2008 Apr;128(4):1050-3.
 		 17914445 
Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet. 2007 Sep;39(9):1120-6.
 		 17704776 
Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, Speleman F, Legius E, Messiaen L. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007 Aug;81(2):243-51.
 		 17668375 
Wimmer K, Roca X, Beiglböck H, Callens T, Etzler J, Rao AR, Krainer AR, Fonatsch C, Messiaen L. Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5' splice-site disruption. Hum Mutat. 2007 Jun;28(6):599-612.  17311297 
Upadhyaya M, Huson SM, Davies M, Thomas N, Chuzhanova N, Giovannini S, Evans DG, Howard E, Kerr B, Griffiths S, Consoli C, Side L, Adams D, Pierpont M, Hachen R, Barnicoat A, Li H, Wallace P, Van Biervliet JP, Stevenson D, Viskochil D, Baralle D, Haan E, Riccardi V, Turnpenny P, Lazaro C, Messiaen L. An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.
Am J Hum Genet. 2007 Jan;80(1):140-51.
 		 17160901 
Maertens O, Brems H, Vandesompele J, De Raedt T, Heyns I, Rosenbaum T, De Schepper S, De Paepe A, Mortier G, Janssens S, Speleman F, Legius E, Messiaen L. Comprehensive NF1 screening on cultured Schwann cells from neurofibromas. Hum Mutat. 2006 Oct;27(10):1030-40.

 		 16941471 
Wimmer K, Yao S, Claes K, Kehrer-Sawatzki H, Tinschert S, De Raedt T, Legius E, Callens T, Beiglböck H, Maertens O, Messiaen L.
Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients. Genes Chromosomes Cancer. 2006 Mar;45(3):265-76.
 		 16283621 
Messiaen LM, Wimmer K. Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1. J Med Genet. 2005 May;42(5):e25.  15863657 
Zatkova A, Messiaen L, Vandenbroucke I, Wieser R, Fonatsch C, Krainer AR, Wimmer K. Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of NF1. Hum Mutat. 2004 Dec;24(6):491-501.
 		 15523642 
Vandenbroucke I, Van Oostveldt P, Coene E, De Paepe A, Messiaen L.
Neurofibromin is actively transported to the nucleus. FEBS Lett. 2004 Feb 27;560(1-3):98-102.
 		 14988005 
Vandenbroucke I, van Doorn R, Callens T, Cobben JM, Starink TM, Messiaen L. Genetic and clinical mosaicism in a patient with neurofibromatosis type 1. Hum Genet. 2004 Feb;114(3):284-90.

 		 14605872 
Vandenbroucke I, Vandesompele J, De Paepe A, Messiaen L. Quantification of NF1 transcripts reveals novel highly expressed splice variants. FEBS Lett. 2002 Jul 3;522(1-3):71-6.
 		 12095621 
Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, De Paepe A. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000;15(6):541-55.


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Keywords
the neurofibromatoses, genetic testing, mosaicism, splicing, RNA-based mutation analysis