CMMC: Cirak, Sebahattin - assoc. JRG 02

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

Pergande M, Motameny S, Özdemir Ö, Kreutzer M, Wang H, Daimagüler HS, Becker K, Karakaya M, Ehrhardt H, Elcioglu N, Ostojic S, Chao CM, Kawalia A, Duman Ö, Koy A, Hahn A, Reimann J, Schoner K, Schänzer A, Westhoff JH, Schwaibold EMC, Cossee M, Imbert-Bouteille M, von Pein H, Haliloglu G, Topaloglu H, Altmüller J, Nürnberg P, Thiele H, Heller R, Cirak S. The genomic and clinical landscape of fetal akinesia. Genet Med. 2019 Nov 4. doi: 10.1038/s41436-019-0680-1. [Epub ahead of print] PubMed PMID: 31680123.
Wang H, Kaçar Bayram A, Sprute R, Ozdemir O, Cooper E, Pergande M, Efthymiou S, Nedic I, Mazaheri N, Stumpfe K, Azizi Malamiri R, Shariati G, Zeighami J, Bayram N, Naghibzadeh SK, Tajik M, Yaşar M, Sami Güven A, Bibi F, Sultan T, Salpietro V, Houlden H, Per H, Galehdari H, Shalbafan B, Jamshidi Y, Cirak S. Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking. Front Neurosci. 2019 Oct 14;13:974. doi: 10.3389/fnins.2019.00974. eCollection 2019. PubMed PMID: 31680794; PubMed Central PMCID: PMC6807680.
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. Erratum in: J Hum Genet. 2019 Aug 6;:. 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.

Publications 2022 as of June 30

Bayram N, Kacar Bayram A, Daimaguler HS, Dafsari HS, Bamborschke D, Uyanik G, Erdogan M, Ozsaygili C, Pangal E, Yuvaci I, Doganay S, Gumus H, Per H, Jungbluth H, and Cirak S (2022). Genotype-phenotype correlations in ocular manifestations of Marinesco-Sjogren syndrome: Case report and literature review. Eur J Ophthalmol32, NP92-NP97. doi:10.1177/11206721211021291.

Fazeli W, Bamborschke D, Moawia A, Bakhtiari S, Tafakhori A, Giersdorf M, Hahn A, Weik A, Kolzter K, Shafiee S, Jin SC, Korber F, Lee-Kirsch MA, Darvish H, Cirak S, Kruer MC, and Koy A (2022). The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature. Eur J Paediatr Neurol36, 7-13. doi:10.1016/j.ejpn.2021.10.011.

Publications 2021

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, Weixler L, 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. 2021 Dec 2;108(12):2385. doi: 10.1016/j.ajhg.2021.11.013. PMID: 34861176

Fazeli W, Bamborschke D, Moawia A, Bakhtiari S, Tafakhori A, Giersdorf M, Hahn A, Weik A, Kolzter K, Shafiee S, Jin SC, Körber F, Lee-Kirsch MA, Darvish H, Cirak S, Kruer MC, Koy A. The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature. Eur J Paediatr Neurol. 2021 Oct 30;36:7-13. doi: 10.1016/j.ejpn.2021.10.011. Epub ahead of print. PMID:34773825.

Kaczmarek AT, Bender D, Gehling T, Kohl JB, Daimagüler HS, Santamaria-Araujo JA, Liebau MC, Koy A, Cirak S, Schwarz G. A defect in molybdenum cofactor binding causes an attenuated form of sulfite oxidase deficiency. J Inherit Metab Dis. 2021 Nov 6. doi: 10.1002/jimd.12454. Epub ahead of print. PMID: 34741542.

Klionsky D.J. et al., (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy 1, 1-382.

Waseem SS, Moawia A, Budde B, Tariq M, Khan A, Ali Z, Khan S, Iqbal M, Malik NA, Haque SU, Altmüller J, Thiele H, Hussain MS, Cirak S, Baig SM, Nürnberg P. A Homozygous AKNA Frameshift Variant Is Associated with Microcephaly in a Pakistani Family. Genes (Basel). 2021 Sep 24;12(10):1494. doi: 10.3390/genes12101494. PMID: 34680889; PMCID: PMC8535656.

Daimagüler HS, Akpulat U, Özdemir Ö, Yis U, Güngör S, Talim B, Diniz G, Baydan F, Thiele H, Altmüller J, Nürnberg P, Cirak S. Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey. Am J Med Genet A. 2021 Jun;185(6):1678-1690. doi: 10.1002/ajmg.a.62148. Epub 2021 Mar 10. PMID: 33694278

Dafsari HS, Becker LL, von der Hagen M, Cirak S. Genomic profiling in neuronal dyneinopathies and updated classifications. Am J Med Genet A. 2021 Aug;185(8):2607-2610. doi: 10.1002/ajmg.a.62243. Epub 2021 May 15. PMID: 33991169

Houge G, Laner A, Cirak S, de Leeuw N, Scheffer H, den Dunnen JT. Stepwise ABC system for classification of any type of genetic variant. Eur J Hum Genet. 2021 May 13. doi: 10.1038/s41431-021-00903-z. Online ahead of print. PMID: 33981013

Bayram N, Kaçar Bayram A, Daimagüler HS, Salimi Dafsari H, Bamborschke D, Uyanik G, Erdogan M, Özsaygılı C, Pangal E, Yuvaci İ, Doğanay S, Gümüş H, Per H, Jungbluth H, Çırak S. Genotype-phenotype correlations in ocular manifestations of Marinesco-Sjögren syndrome: Case report and literature review.Eur J Ophthalmol. 2021 Jun 2:11206721211021291. doi: 10.1177/11206721211021291. Online ahead of print. PMID: 34075802

Bamborschke D, Kreutzer M, Koy A, Koerber F, Lucas N, Huenseler C, Herkenrath P, Lee-Kirsch MA, Cirak S. PNPT1 mutations may cause Aicardi-Goutières-Syndrome. Brain Dev. 2021 Feb;43(2):320-324. doi: 10.1016/j.braindev.2020.10.005. Epub 2020 Nov 4. PMID: 33158637

Sprute R, Jergas H, Ölmez A, Alawbathani S, Karasoy H, Dafsari HS, Becker K, Daimagüler HS, Nürnberg P, Muntoni F, Topaloglu H, Uyanik G, Cirak S. Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations. Am J Med Genet A. 2021 Feb;185(2):344-354. doi: 10.1002/ajmg.a.61951. Epub 2020 Nov 5. PMID: 33155358

Rees M, Nikoopour R, Fukuzawa A, Kho AL, Fernandez-Garcia MA, Wraige E, Bodi I, Deshpande C, Özdemir Ö, Daimagüler HS, Pfuhl M, Holt M, Brandmeier B, Grover S, Fluss J, Longman C, Farrugia ME, Matthews E, Hanna M, Muntoni F, Sarkozy A, Phadke R, Quinlivan R, Oates EC, Schröder R, Thiel C, Reimann J, Voermans N, Erasmus C, Kamsteeg EJ, Konersman C, Grosmann C, McKee S, Tirupathi S, Moore SA, Wilichowski E, Hobbiebrunken E, Dekomien G, Richard I, Van den Bergh P, Domínguez-González C, Cirak S, Ferreiro A, Jungbluth H, Gautel M. Making sense of missense variants in TTN-related congenital myopathies. Acta Neuropathol. 2021 Mar;141(3):431-453. doi: 10.1007/s00401-020-02257-0. Epub 2021 Jan 15. PMID: 33449170

Bamborschke D, Özdemir Ö, Kreutzer M, Motameny S, Thiele H, Kribs A, Dötsch J, Altmüller J, Nürnberg P, Cirak S. Ultra-rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours. Am J Med Genet A. 2021 Jan;185(1):90-96. doi: 10.1002/ajmg.a.61917. Epub 2020 Oct 13. PMID: 33048476

Publications 2020

Paketci C, Karakaya M, Edem P, Bayram E, Keller N, Daimagüler HS, Cirak S, Jordanova A, Hiz S, Wirth B, Yiş U. Clinical, electrophysiological and genetic characteristics of childhood hereditary polyneuropathies. Rev Neurol (Paris). 2020 Dec;176(10):846-855. doi: 10.1016/j.neurol.2020.04.016. Epub 2020 Jul 21. PMID: 32709422

Becker LL, Dafsari HS, Schallner J, Abdin D, Seifert M, Petit F, Smol T, Bok L, Rodan L, Krapels I, Spranger S, Weschke B, Johnson K, Straub V, Kaindl AM, Di Donato N, von der Hagen M, Cirak S. The clinical-phenotype continuum in DYNC1H1-related disorders-genomic profiling and proposal for a novel classification. J Hum Genet. 2020 Nov;65(11):1003-1017. doi: 10.1038/s10038-020-0803-1. Epub 2020 Aug 12. PMID: 32788638

Bamborschke D, Daimagüler HS, Hahn A, Hussain MS, Nürnberg P, Cirak S. Mutation in CEP135 causing primary microcephaly and subcortical heterotopia. Am J Med Genet A. 2020 Oct;182(10):2450-2453. doi: 10.1002/ajmg.a.61762. Epub 2020 Jul 9. PMID: 32643282

Hanzlikova H, Prokhorova E, Krejcikova K, Cihlarova Z, Kalasova I, Kubovciak J, Sachova J, Hailstone R, Brazina J, Ghosh S, Cirak S, Gleeson JG, Ahel I, Caldecott KW. Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair.Nat Commun. 2020 Jul 7;11(1):3391. doi: 10.1038/s41467-020-17069-9. PMID: 32636369

Spitali P, Zaharieva I, Bohringer S, Hiller M, Chaouch A, Roos A, Scotton C, Claustres M, Bello L, McDonald CM, Hoffman EP; CINRG Investigators, Koeks Z, Eka Suchiman H, Cirak S, Scoto M, Reza M, 't Hoen PAC, Niks EH, Tuffery-Giraud S, Lochmüller H, Ferlini A, Muntoni F, Aartsma-Rus A. TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy. Eur J Hum Genet. 2020 Jun;28(6):815-825. doi: 10.1038/s41431-019-0563-6. Epub 2020 Jan 2. PMID: 31896777

Publications 2019

Okur D, Daimagüler HS, Danyeli AE, Tekgül H, Wang H, Wunderlich G, Çırak S, Yiş U. Bi-allelic mutations in PRUNE lead to neurodegeneration with spinal motor neuron involvement and hyperCKaemia. Turk J Pediatr. 2019;61(6):931-936. doi: 10.24953/turkjped.2019.06.015. PMID: 32134588

Dafsari HS, Kocaturk NM, Daimagüler HS, Brunn A, Dötsch J, Weis J, Deckert M, Cirak S. Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B are a cause for congenital myopathy. Acta Neuropathol Commun. 2019 Dec 18;7(1):211. doi: 10.1186/s40478-019-0869-1. PMID: 31852522

Dafsari HS, Kawalia A, Sprute R, Karakaya M, Malenica A, Herkenrath P, Nürnberg P, Motameny S, Thiele H, Cirak S. Novel mutations in SLC6A5 with benign course in hyperekplexia. Cold Spring Harb Mol Case Stud. 2019 Dec 13;5(6):a004465. doi: 10.1101/mcs.a004465. Print 2019 Dec. PMID: 31604777

Naumann M, Peikert K, Günther R, van der Kooi AJ, Aronica E, Hübers A, Danel V, Corcia P, Pan-Montojo F, Cirak S, Haliloglu G, Ludolph AC, Goswami A, Andersen PM, Prudlo J, Wegner F, Van Damme P, Weishaupt JH, Hermann A. Phenotypes and malignancy risk of different FUS mutations in genetic amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2019 Dec;6(12):2384-2394. doi: 10.1002/acn3.50930. Epub 2019 Nov 4. PMID: 31682085

Wang H, Kaçar Bayram A, Sprute R, Ozdemir O, Cooper E, Pergande M, Efthymiou S, Nedic I, Mazaheri N, Stumpfe K, Azizi Malamiri R, Shariati G, Zeighami J, Bayram N, Naghibzadeh SK, Tajik M, Yaşar M, Sami Güven A, Bibi F, Sultan T, Salpietro V, Houlden H, Per H, Galehdari H, Shalbafan B, Jamshidi Y, Cirak S. Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking. Front Neurosci. 2019 Oct 14;13:974. doi: 10.3389/fnins.2019.00974. eCollection 2019. PMID: 31680794

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. PMID: 31165786

Publications 2018

Yiş U, Diniz G, Hazan F, Daimagüler HS, Baysal BT, Baydan F, Akinci G, Ünalp A, Aktan G, Bayram E, Hiz S, Paketçi C, Okur D, Özer E, Danyeli AE, Polat M, Uyanik G, Çirak S. Childhood onset limb-girdle muscular dystrophies in the Aegean part of Turkey.Acta Myol. 2018 Sep 1;37(3):210-220. eCollection 2018 Sep. PMID: 30838351

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. PMID: 30396145

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. PMID: 30157964

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. PMID: 30131190

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. PMID: 29088354