Pauli Research Group

Dr. rer. nat. Roser Ufartes

Regina Grün
MSc student

Prof. Dr. med. Silke Pauli
Group leader





    • Functional studies elucidating a common pathomechanism of CHARGE syndrome and Kabuki syndrome
    • Research on the function of class 3 semaphorins in the development and pathogenesis of syndromic disorders
    • Molecular studies on FBRSL1 and its role in the pathogenesis of a novel syndromic phenotype


Functional studies elucidating a common pathomechanism of CHARGE syndrome and Kabuki syndrome

CHARGE syndrome (OMIM 214800), like Kabuki syndrome (OMIM 147920, 300867), is a clinically heterogeneous and complex dysmorphic syndrome. Mutations in the chromatin remodeler CHD7 are causative of CHARGE syndrome, while pathogenic variants in the chromatin modification proteins KMT2D and KDM6A are identified in Kabuki syndrome patients. Depending on the observed combination of malformations, the two syndromes can show strongly overlapping phenotypes. Especially during infancy and early childhood, when the typical Kabuki facies has not yet fully evolved, it can be difficult to distinguish the two disorders clinically. Their similar phenotypes might be due to the fact that KMT2D, KDM6A and CHD7 all act in the same chromatin modification and remodelling machinery. Our DFG-funded project aims to reveal a common pathogenic mechanism of these two syndromes.

Research on the function of class 3 semaphorins in the development and pathogenesis of syndromic disorders

Semaphorins are a group of transmembrane or secreted proteins which act, for example, as signaling molecules to guide sprouting axons. Additionally, they play a role in development due to their involvement in the migration of neural crest cells, angiogenesis, and bone formation, and other processes. Based on their domain structure and sequence homologies, semaphorins are grouped into subclasses. Our research group focuses on class 3 semaphorins. Our aim is to explore the function of these proteins in the pathogenesis of syndromic disorders. To answer this question we perform cell culture experiments, use molecular methods, and apply NGS-based approaches.

Molecular studies on FBRSL1 and its role in the pathogenesis of a novel syndromic disorder

We have recently associated truncating mutations in a specific region of FBRSL1 with a novel syndromic disorder. The clinical features include cleft palate, heart defects, respiratory insufficiency, swallowing difficulty, distinctive skin creases regressing in the first year of life, microcephaly, and severe global developmental delay. In our DFG-funded project, we focus on a deeper characterization of the newly identified malformation syndrome and the identification of the role of FBRSL1 in its pathogenesis.

Publications Pauli Research Group





2016 and before


De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome
Ufartes R, Berger H, Till K, Salinas G, Sturm M, Altmüller J, Nürnberg P, Thiele H, Funke R, Apeshiotis N, Langen H, Wollnik B, Borchers A, Pauli S.
Hum Genet. 2020 May 18.

A Novel Mutation in PIGA Associated with Multiple Congenital Anomalies-Hypotonia-Seizure Syndrome 2 (MCAHS2) in a Boy with a Combination of Severe Epilepsy and Gingival Hyperplasia
Neuhofer CM, Funke R, Wilken B, Knaus A, Altmüller J, Nürnberg P, Li Y, Wollnik B, Burfeind P, Pauli S.
Mol Syndromol. 2020 11:30-37.


X-linked myotubular myopathy and recurrent spontaneous pneumothorax: A new phenotype?
Carstens PO, Schwaibold EMC, Schregel K, Obermaier CD, Wrede A, Zechel S, Pauli S, Schmidt J.
Neurol Genet. 2019 5:e327.

Homozygosity for the c.428delG variant in KIAA0586 in a healthy individual: implications for molecular testing in patients with Joubert syndrome
Pauli S, Altmüller J, Schröder S, Ohlenbusch A, Dreha-Kulaczewski S, Bergmann C, Nürnberg P, Thiele H, Li Y, Wollnik B, Brockmann K
J Med Genet. 2019 56:261-264.


Sema3a plays a role in the pathogenesis of CHARGE syndrome
Ufartes R, Schwenty-Lara J, Freese L, Neuhofer C, Möller J, Wehner P, van Ravenswaaij-Arts CMA, Wong MTY, Schanze I, Tzschach A, Bartsch O, Borchers A, Pauli S
Hum Mol Genet. 2018 27:1343-1352.

Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22
Schnabel F, Smogavec M, Funke R, Pauli S, Burfeind P, Bartels I
Mol Cytogenet 2018 11:62.


Novel fukutin mutations in limb-girdle muscular dystrophy type 2M with childhood onset
Smogavec M, Zschüntzsch J, Kress W, Mohr J, Hellen P, Zoll B, Pauli S, Schmidt J.
Neurol Genet. 2017 Jul 10;3(4):e167.

CHARGEd with neural crest defects
Pauli S., Bajpai R., Borchers A.
Am J Med Genet Part C. Semin Med Genet. 2017 175:478-486.

2016 and before

Uniparental Trisomy of a Mutated HRAS Proto-Oncogene in Embryonal Rhabdomyosarcoma of a Patient With Costello Syndrome
Menke J, Pauli S, Sigler M, Kühnle I, Shoukier M, Zoll B, Ganster C, Salinas-Riester G, Schaefer IM
J Clin Oncol. 2015 3:e62-5, doi: 10.1200/JCO.2013.49.6539. Epub 2014 Mar 17.

Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
Kratz CP, Franke L, Peters H, Kohlschmidt N, Kazmierczak B, Finckh U, Bier A, Eichhorn B, Blank C, Kraus C, Kohlhase J, Pauli S, Wildhardt G, Kutsche K, Auber B, Christmann A, Bachmann N, Mitter D, Cremer FW, Mayer K, Daumer-Haas C, Nevinny-Stickel-Hinzpeter C, Oeffner F, Schlüter G, Gencik M, Überlacker B, Lissewski C, Schanze I, Greene MH, Spix C, Zenker M
Br J Cancer. 2015 112:1392-7.

Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations
Martinelli S, Stellacci E, Pannone L, D’Agostino D, Consoli F, Lissewski C, Silvano M, Cencelli G, Lepri F, Maitz S, Pauli S, Rauch A, Zampino G, Selicorni A, Melançon S, Digilio MC, Gelb BD, De Luca A, Dallapiccola B, Zenker M, Tartaglia M
Hum Mutat. 2015 36:787-96.

Intragenic duplication of EHMT1 gene results in Kleefstra syndrome
Schwaibold EM, Smogavec M, Hobbiebrunken E, Winter L, Zoll B, Burfeind P, Brockmann K, Pauli S
Mol Cytogenet. 2014 23;7(1): 74.

CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance
Schulz Y, Wehner P, Opitz L, Salinas-Riester G, Bongers EM, van Ravenswaaij-Arts CM, Wincent J, Schoumans J, Kohlhase J, Borchers A, Pauli S
Hum Genet. 2014 Aug;133(8):997-1009.

CHARGE and Kabuki syndromes: a phenotypic and molecular link
Schulz Y, Freese L, Mänz J, Zoll B, Völter C, Brockmann K, Bögershausen N, Becker J, Wollnik B, Pauli S
Hum Mol Genet. 2014 15;23(16): 4396-405.

High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one-third of probands are minors
Spiegler S, Najm J, Liu J, Gkalympoudis S, Schröder W, Borck G, Brockmann K, Elbracht M, Fauth C, Ferbert A, Freudenberg L, Grasshoff U, Hellenbroich Y, Henn W, Hoffjan S, Hüning I, Korenke GC, Kroisel PM, Kunstmann E, Mair M, Munk-Schulenburg S, Nikoubashman O, Pauli S, Rudnik-Schöneborn S, Sudholt I, Sure U, Tinschert S, Wiednig M, Zoll B, Ginsberg MH, Felbor U
Mol Genet Genomic Med. 2014 2(2):176-85.

Acute onset of adult Alexander disease
Schmidt H, Kretzschmar B, Lingor P, Pauli S, Schramm P, Otto M, Ohlenbusch A, Brockmann K
J Neurol Sci. 2013 331:152-4

Soft tissue perineurioma and other unusual tumors in a patient with neurofibromatosis type 1
Schaefer IM, Ströbel P, Thiha A, Sohns JM, Mühlfeld C, Küffer S, Felmerer G, Stepniewski A, Pauli S, Agaimy A
Int J Clin Exp Pathol. 2013 6:3003-8. eCollection 2013

CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin
Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J
Clin Genet. 2012 81:234-239

Occurrence of acute lymphoblastic leukemia and juvenile myelomonocytic leukemia in a patient with Noonan syndrome carrying the germline PTPN11 mutation p.E139D
Pauli S, Steinemann D, Dittmann K, Wienands J, Shoukier M, Möschner M, Burfeind P, Manukjan G, Göhring G, Escherich G
Am J Med Genet A. 2012 158A:652-658.

Discordant phenotype in monozygotic twins with mosaic trisomy 12p in lymphocytes
Pauli S, Schmidt T, Funke R, Zoll B, Burfeind P, Dybowski U, Shoukier M, Bartels I
Eur J Med Genet. 2012 55:480-484.

Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex
Batsukh T, Schulz Y, Wolf S, Rabe TI, Oellerich T, Urlaub H, Schaefer IM, Pauli S
PLoS One. 2012 7(12):e52640

The face of Noonan syndrome: Does phenotype predict genotype
Allanson JE, Bohring A, Dörr HG, Dufke A, Gillessen-Kaesbach G, Horn D, König R, Kratz CP, Kutsche K, Pauli S, Raskin S, Rauch A, Turner A, Wieczorek D, Zenker M
Am J Med Genet A. 2010 152A:1960-1966.

CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome
Batsukh T, Pieper L, Koszucka AM, von Velsen N, Hoyer-Fender S, Elbracht M, Bergman JE, Hoefsloot LH, Pauli S
Hum Mol Genet. 2010 19:2858-66

Proven germline mosaicism in a father of two children with CHARGE syndrome
Pauli S, Pieper L, Häberle J, Grzmil P, Burfeind P, Steckel M, Lenz U, Michelmann HW
Clin Genet. 2009 75:473-479

TC II deficiency: avoidance of false negative molecular genetics by RNA based investigations
Häberle J, Pauli S, Berning C, Koch HG, Linnebank M
J Hum Genet. 2009 54:331-334

Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia
Pantakani DV, Zechner U, Arygriou L, Pauli S, Sauter SM, Mannan AU
Clin Genet. 2008 73:268-272.

Investigation of citrullinemia type I variants by in vitro expression studies
Berning C, Bieger I, Pauli S, Vermeulen T, Vogl T, Rummel T, Höhne W, Koch HG, Rolinski B,Gempel K, Häberle J
Hum Mutat. 2008 29:1222-1227

Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene
Pauli S, Söker T, Klopp N, Illig T, Engel W, Graw J
Mol Vis. 2007 13:962-967.

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome
Zenker M, Horn D, Wieczorek D, Allanson J, Pauli S, van der Burgt I, Doerr HG, Gaspar H, Hofbeck M, Gillessen-Kaesbach G, Koch A, Meinecke P, Mundlos S, Nowka A, Rauch A, Reif S, von Schnakenburg C,Seidel H, Wehner LE, Zweier C,Bauhuber S, Matejas V, Kratz CP, Thomas C, Kutsche K
J Med Genet. 2007 44:651-656.

Identification of novel mutations of the human N-acetylglutamate synthase gene and their functional investigation by expression studies
Schmidt E, Nuoffer JM, Häberle J, Pauli S, Guffon N, Vianey-Saban C, Wermuth B, Koch HG
Biochim Biophys Acta. 2005 1740:54-59.

Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset
Häberle J, Schmidt E, Pauli S, Rapp B, Christensen E, Wermuth B, Koch HG
Hum Mutat. 2003 21:444

Mutation analysis in patients with N-acetylglutamate synthase deficiency
Häberle J, Schmidt E, Pauli S, Kreuder JG, Plecko B, Galler A, Wermuth B, Harms E, Koch HG
Hum Mutat 2003 21:593-7

Mild citrullinemia in caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1)
Häberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG
Mol Genet Metab. 2003 80:302-306.

Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia
Häberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ. Harms E. Koch HG.
Hum Genet. 2002 110:327-333

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