Sebahattin Cirak - assoc. JRG II

Primary Muscle Disease

Group research focus
Disease gene discovery for muscular dystrophies, myopathies and brain malformations.
Molecular disease mechanisms in congenital muscular dystrophies in particular dystroglycanopathies.
Protein biochemistry of enzymes involved in dystroglycan glycosylation and its translational application.

Translational research, natural history and biomarkers discovery for CMD and LGMD.
Natural history studies  and Biomarker discovery for DMD.
RNA therapeutics and further development of exon skipping therapies for DMD.

Selected publications 2019

Dafsari HS, Sprute R, Wunderlich G, Daimagüler HS, Karaca E, Contreras A, Becker K, Schulze-Rhonhof M, Kiening K, Karakulak T, Kloss M, Horn A, Pauls A, Nürnberg P, Altmüller J, Thiele H, Assmann B, Koy A, Cirak S. Novel mutations in KMT2B offer pathophysiological insights into childhood-onset progressive dystonia. J Hum Genet. 2019 Aug;64(8):803-813. doi: 10.1038/s10038-019-0625-1. Epub 2019 Jun 5. PubMed PMID: 31165786.

Bender D, Kaczmarek AT, Santamaria-Araujo JA, Stueve B, Waltz S, Bartsch D, Kurian L, Cirak S, Schwarz G. Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Hum Mol Genet. 2019 May 25. pii: ddz109. doi: 10.1093/hmg/ddz109. [Epub ahead of print] PubMed PMID: 31127934.

Selected publications 2018

Akpulat U, Wang H, Becker K, Contreras A, Partridge TA, Novak JS, Cirak S. Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD. Mol Ther Nucleic Acids. 2018 Dec 7;13:534-542. doi: 10.1016/j.omtn.2018.10.002. Epub 2018 Oct 10. PubMed PMID: 30396145; PubMed Central PMCID: PMC6222172.

Fazeli W, Becker K, Herkenrath P, Düchting C, Körber F, Landgraf P, Nürnberg P, Altmüller J, Thiele H, Koy A, Liebau MC, Simon T, Dötsch J, Cirak S. Dominant SCN2A Mutation Causes Familial Episodic Ataxia and Impairment of Speech Development. Neuropediatrics. 2018 Aug 30. doi: 10.1055/s-0038-1668141. [Epub ahead of print] PubMed PMID: 30165711.

Wang H, Schänzer A, Kampschulte B, Daimagüler HS, Logeswaran T, Schlierbach H, Petzinger J, Ehrhardt H, Hahn A, Cirak S. A novel SPEG mutation causes non-compaction cardiomyopathy and neuropathy in a floppy infant with centronuclear myopathy. Acta Neuropathol Commun. 2018 Aug 29;6(1):83. doi: 10.1186/s40478-018-0589-y. PubMed PMID: 30157964; PubMed Central PMCID: PMC6114030.

Thangarajh M, Elfring GL, Trifillis P, McIntosh J, Peltz SW; Ataluren Phase 2b Study Group. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy. Neurology. 2018 Aug 22. pii: 10.1212/WNL.0000000000006245. doi: 10.1212/WNL.0000000000006245. [Epub ahead of print] PubMed PMID: 30135256.

Ullmann U, D'Argenzio L, Mathur S, Whyte T, Quinlivan R, Longman C, Farrugia ME, Manzur A, Willis T, Jungbluth H, Pitt M, Cirak S; UK10K consortium, Feng L, Stewart W, Mein R, Phadke R, Sewry C, Sarkozy A, Muntoni F. ECEL1 gene related contractural syndrome: Long-term follow-up and update on clinical and pathological aspects. Neuromuscul Disord. 2018 Sep;28(9):741-749. doi: 10.1016/j.nmd.2018.05.012. Epub 2018 Jun 30. PubMed PMID: 30131190.

Koy A, Cirak S, Gonzalez V, Becker K, Roujeau T, Milesi C, Baleine J, Cambonie G, Boularan A, Greco F, Perrigault PF, Cances C, Dorison N, Doummar D, Roubertie A, Beroud C, Körber F, Stüve B, Waltz S, Mignot C, Nava C, Maarouf M, Coubes P, Cif L. Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia. J Neurol Sci. 2018 Aug 15;391:31-39. doi: 10.1016/j.jns.2018.05.018. Epub 2018 May 22. PubMed PMID: 30103967.

Ghosh SG, Becker K, Huang H, Salazar TD, Chai G, Salpietro V, Al-Gazali L, Waisfisz Q, Wang H, Vaux KK, Stanley V, Manole A, Akpulat U, Weiss MM, Efthymiou S, Hanna MG, Minetti C, Striano P, Pisciotta L, De Grandis E, Altmüller J, Nürnberg P, Thiele H, Yis U, Okur TD, Polat AI, Amiri N, Doosti M, Karimani EG, Toosi MB, Haddad G, Karakaya M, Wirth B, van Hagen JM, Wolf NI, Maroofian R, Houlden H, Cirak S, Gleeson JG. Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome. Am J Hum Genet. 2018 Sep 6;103(3):431-439. doi: 10.1016/j.ajhg.2018.07.010. Epub 2018 Aug 9. PubMed PMID: 30100084; PubMed Central PMCID: PMC6128219.

Wunderlich G, Brunn A, Daimagüler HS, Bozoglu T, Fink GR, Lehmann HC, Weis J, Cirak S. Long term history of a congenital core-rod myopathy with compound heterozygous mutations in the Nebulin gene. Acta Myol. 2018 Jun 1;37(2):121-127. eCollection 2018 Jun. PubMed PMID: 30057997; PubMed Central PMCID: PMC6060425.

Stark C, Duran I, Cirak S, Hamacher S, Hoyer-Kuhn HK, Semler O, Schoenau E. Vibration-Assisted Home Training Program for Children With Spinal Muscular Atrophy. Child Neurol Open. 2018 Jun 10;5:2329048X18780477. doi: 10.1177/2329048X18780477. eCollection 2018. PubMed PMID: 29977975; PubMed Central PMCID: PMC6024344.

Wunderlich G, Abicht A, Brunn A, Daimagüler HS, Schroeter M, Fink GR, Lehmann HC, Cirak S. [Congenital myasthenic syndromes in adulthood : Challenging, rare but treatable]. Nervenarzt. 2018 Jul 4. doi: 10.1007/s00115-018-0562-9. [Epub ahead of print] Review. German. PubMed PMID: 29974128.

Broekaert IJ, Becker K, Gottschalk I, Körber F, Dötsch J, Thiele H, Altmüller J, Nürnberg P, Hünseler C, Cirak S. Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy. J Med Genet. 2018 Sep;55(9):637-640. doi: 10.1136/jmedgenet-2018-105262. Epub 2018 Apr 16. PubMed PMID: 29661969.

Bamborschke D, Pergande M, Becker K, Koerber F, Dötsch J, Vierzig A, Weber LT, Cirak S. A novel mutation in sphingosine-1-phosphate lyase causing congenital brain malformation. Brain Dev. 2018 Jun;40(6):480-483. doi: 10.1016/j.braindev.2018.02.008. Epub 2018 Mar 2. PubMed PMID: 29501407.

Alawbathani S, Kawalia A, Karakaya M, Altmüller J, Nürnberg P, Cirak S. Late diagnosis of a truncating WISP3 mutation entails a severe phenotype of progressive pseudorheumatoid dysplasia. Cold Spring Harb Mol Case Stud. 2018 Feb 1;4(1). pii: a002139. doi: 10.1101/mcs.a002139. Print 2018 Feb. PubMed PMID: 29258992; PubMed Central PMCID: PMC5793772.

Selected publications 2017

Yis U, Dixit V, Isikay S, Karakaya M, Baydan F, Diniz G, Polat I, Hiz-Kurul S, Çirak S. Occipital cortex dysgenesis with white matter changes due to mutations in Laminin a2. Turk J Pediatr. 2017;59(3):338-341. doi: 10.24953/turkjped.2017.03.018. PubMed PMID: 29376585.

Yis U, Becker K, Çirak S. A boy with neck weakness. Neuromuscul Disord. 2018 Mar;28(3):236-237. doi: 10.1016/j.nmd.2017.11.016. Epub 2017 Dec 5. PubMed PMID: 29339009.

Wang H, Salter CG, Refai O, Hardy H, Barwick KES, Akpulat U, Kvarnung M, Chioza BA, Harlalka G, Taylan F, Sejersen T, Wright J, Zimmerman HH, Karakaya M, Stüve B, Weis J, Schara U, Russell MA, Abdul-Rahman OA, Chilton J, Blakely RD, Baple EL, Cirak S, Crosby AH. Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization. Brain. 2017 Nov 1;140(11):2838-2850. doi: 10.1093/brain/awx249. PubMed PMID: 29088354; PubMed Central PMCID: PMC5844214.

Novak JS, Hogarth MW, Boehler JF, Nearing M, Vila MC, Heredia R, Fiorillo AA, Zhang A, Hathout Y, Hoffman EP, Jaiswal JK, Nagaraju K, Cirak S, Partridge TA. Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle. Nat Commun. 2017 Oct 16;8(1):941. doi: 10.1038/s41467-017-00924-7. Erratum in: Nat Commun. 2018 Jan 15;9(1):208. Nat Commun. 2018 Mar 23;9(1):1256. PubMed PMID: 29038471; PubMed Central PMCID: PMC5643396. Author Correction: Nat Commun. 2018 Mar 23;9(1):1256. PubMed PMID: 29038471; PubMed Central PMCID: PMC5643396.

Shamseldin HE, Kurdi W, Almusafri F, Alnemer M, Alkaff A, Babay Z, Alhashem A, Tulbah M, Alsahan N, Khan R, Sallout B, Al Mardawi E, Seidahmed MZ, Meriki N, Alsaber Y, Qari A, Khalifa O, Eyaid W, Rahbeeni Z, Kurdi A, Hashem M, Alshidi T, Al-Obeid E, Abdulwahab F, Ibrahim N, Ewida N, El-Akouri K, Al Mulla M, Ben-Omran T, Pergande M, Cirak S, Al Tala S, Shaheen R, Faqeih E, Alkuraya FS. Molecular autopsy in maternal-fetal medicine. Genet Med. 2018 Apr;20(4):420-427. doi: 10.1038/gim.2017.111. Epub 2017 Jul 20. PubMed PMID: 28749478.

Hendricks AE, Bochukova EG, Marenne G, Keogh JM, Atanassova N, Bounds R, Wheeler E, Mistry V, Henning E, Körner A, Muddyman D, McCarthy S, Hinney A, Hebebrand J, Scott RA, Langenberg C, Wareham NJ, Surendran P, Howson JM, Butterworth AS, Danesh J, Nordestgaard BG, Nielsen SF, Afzal S, Papadia S, Ashford S, Garg S, Millhauser GL, Palomino RI, Kwasniewska A, Tachmazidou I, O'Rahilly S, Zeggini E, Barroso I, Farooqi IS; Understanding Society Scientific Group; EPIC-CVD Consortium; UK10K Consortium. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity. Sci Rep. 2017 Jun 29;7(1):4394. doi: 10.1038/s41598-017-03054-8. PubMed PMID: 28663568; PubMed Central PMCID: PMC5491520.

Selected publications 2016

Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmüller H, Straub V, Bushby K, Castrignanò T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang X, Hodge B, Esser KA, Ferlini A. Deep RNA profiling identified clock and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016 Mar 4. pii: jcs.175927.[Epub ahead of print]

Jansen JC, Cirak S, van Scherpenzeel M, Timal S, Reunert J, Rust S, Pérez B, Vicogne D, Krawitz P, Wada Y, Ashikov A, Pérez-Cerdá C, Medrano C, Arnoldy A, Hoischen A, Huijben K, Steenbergen G, Quelhas D, Diogo L, Rymen D, Jaeken J, Guffon N, Cheillan D, van den Heuvel LP, Maeda Y, Kaiser O, Schara U, Gerner P, van den Boogert MA, Holleboom AG, Nassogne MC, Sokal E, Salomon J, van den Bogaart G, Drenth JP, Huynen MA, Veltman JA, Wevers RA, Morava E, Matthijs G, Foulquier F, Marquardt T, Lefeber DJ. CCDC115 Deficiency Causes a Disorder ofGolgi Homeostasis with Abnormal Protein Glycosylation. Am J Hum Genet. 2016 Feb4;98(2):310-21.

Willkomm L, Heredia R, Hoffmann K, Wang H, Voit T, Hoffman EP, Cirak S. Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia. J Hum Genet. 2016 Feb 18.

Chamova T, Guergueltcheva V, Gospodinova M, Krause S, Cirak S, Kaprelyan A, Angelova L, Mihaylova V, Bichev S, Chandler D, Naydenov E, Grudkova M, Djukmedzhiev P, Voit T, Pogoryelova O, Lochmüller H, Goebel HH, Bahlo M, Kalaydjieva L, Tournev I. GNE myopathy in Roma patients homozygous for the p.I618T founder mutation. Neuromuscul Disord. 2015 Sep;25(9):713-8. 

Huang J, Howie B, McCarthy S, Memari Y, Walter K, Min JL, Danecek P, Malerba G, Trabetti E, Zheng HF; UK10K Consortium (including Cirak S), Gambaro G, Richards JB, Durbin R, Timpson NJ, Marchini J, Soranzo N. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nat Commun. 2015 Sep 14;6:8111.

Schmidts M, Hou Y, Cortés CR, Mans DA, Huber C, Boldt K, Patel M, van Reeuwijk J, Plaza JM, van Beersum SE, Yap ZM, Letteboer SJ, Taylor SP, Herridge W, Johnson CA, Scambler PJ, Ueffing M, Kayserili H, Krakow D, King SM; UK10K (including Cirak S), Beales PL, Al-Gazali L, Wicking C, Cormier-Daire V, Roepman R, Mitchison HM, Witman GB. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nat Commun. 2015 Jun 5;6:7074.

Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ, Mullin BH, Shihab HA, Min J, Walter K, Memari Y, Huang J, Barnes MR, Beilby JP, Charoen P, Danecek P, Dudbridge F, Forgetta V, Greenwood C, Grundberg E, Johnson AD, Hui J, Lim EM, McCarthy S, Muddyman D, Panicker V, Perry JR, Bell JT, Yuan W, Relton C, Gaunt T, Schlessinger D, Abecasis G, Cucca F, Surdulescu GL, Woltersdorf W, Zeggini E, Zheng HF, Toniolo D, Dayan CM, Naitza S, Walsh JP, Spector T, Davey Smith G, Durbin R, Richards JB, Sanna S, Soranzo N, Timpson NJ, Wilson SG; UK0K Consortium (including Cirak S) Whole-genome sequence-based analysis of thyroid function. Nat Commun. 2015 Mar 6;6:5681.

UK10K Consortium (including Cirak S), Walter K, Min JL, Huang J, Crooks L, Memari Y, McCarthy S, Perry JR, Xu C, Futema M, Lawson D, Iotchkova V, Schiffels S, Hendricks AE, Danecek P, Li R, Floyd J, Wain LV, Barroso I, Humphries SE, Hurles ME, Zeggini E, Barrett JC, Plagnol V, Richards JB, Greenwood CM, Timpson NJ, Durbin R, Soranzo N. The UK10K project identifies rare variants in health and disease. Nature. 2015 Oct 1;526(7571):82-90.

Selected publications 2014

Hathout Y, Marathi RL, Rayavarapu S, Zhang A, Brown KJ, Seol H, Gordish-Dressman H, Cirak S, Bello L, Nagaraju K, Partridge T, Hoffman EP, Takeda S, Mah JK, Henricson E, McDonald C.Discovery of Serum Protein Biomarkers in the mdx mouse model and cross-species comparison to Duchenne Muscular Dystrophy patients.Hum Mol Genet.2014 Dec 15;23(24):6458-69. doi: 10.1093/hmg/ddu366. Epub 2014 Jul 15.

Ayoglu B, Chaouch A, Lochmüller H, Politano L, Bertini E, Spitali P, Hiller M,Niks EH, Gualandi F, Pontén F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y,Straub V, Uhlén M, Cirak S, 't Hoen PA, Muntoni F, Ferlini A, Schwenk JM, NilssonP, Al-Khalili Szigyarto C.Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014 Jun 11;6(7):918-36.

Rainger J, Pehlivan D, Johansson S, Bengani H, Sanchez-Pulido L, WilliamsonKA, Ture M, Barker H,Rosendahl K, Spranger J, Horn D, Meynert A, Floyd JA,Prescott T, Anderson CA, Rainger JK, Karaca E, Gonzaga-Jauregui C, Jhangiani S, Muzny DM, Seawright A, Soares DC, Kharbanda M, Murday V, Finch A; UK10K (including Cirak S); Baylor-Hopkins Center for Mendelian Genomics, Gibbs RA, van Heyningen V, Taylor MS, Yakut T, Knappskog PM, Hurles ME, Ponting CP, Lupski JR, Houge G, FitzPatrick DR. Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations. Am J Hum Genet. 2014 Jun 5;94(6):915-23. doi: 10.1016/j.ajhg.2014.05.005.

Lu QL, Cirak S, Partridge T. What Can We Learn From Clinical Trials of Exon Skipping for DMD? Mol Ther Nucleic Acids. 2014 Mar 11;3:e152. doi: 10.1038/mtna.2014.6.

Williamson KA, Rainger J, Floyd JA, Ansari M, Meynert A, Aldridge KV, Rainger JK, Anderson CA, Moore AT, Hurles ME, Clarke A, van Heyningen V, Verloes A, Taylor MS, Wilkie AO; UK10K Consortium (including Cirak S), Fitzpatrick DR. Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects. Am J Hum Genet. 2014 Feb 6;94(2):295-302. doi: 10.1016/j.ajhg.2014.01.001. Epub 2014 Jan 23.


Dr. Sebahattin Cirak

Dept. for Pediatrics and Adolescent Medicine / RG location - CMMC Building

Dr. Sebahattin Cirak

Work +49 221 478 4693

Center of Pediatrics and Adolescent Medicine
Kerpener Str. 34
50931 Cologne

https://kinderklinik.uk-koeln.de/erkrankungen-therapien/muskelzentrum/

Robert-Koch-Str. 21
50931 Cologne

Publications - Sebahattin Cirak

Link to PubMed