Naše laboratoř je součástí Ústavu biologie a lékařské genetiky 2. LF UK a FN Motol. V rámci výzkumných projektů se věnujeme molekulárně genetickým analýzám vzorků DNA dětí s různými vzácnými neurovývojovými poruchami, nejčastěji s opožděným psychomotorickým vývojem, intelektovou nedostatečností, poruchami vývoje řeči, poruchami chování a širokým spektrem dalších přidružených vývojových vad. Jde o velkou skupinou vzácných onemocnění (rare diseases), která jsou způsobena defekty v tisících různých genech. Ve svých výzkumných projektech využíváme metody sekvenování nové generace (NGS), především celoexomové sekvenování (WES), celogenomové sekvenování (WGS) či RNA Seq. Analýzou exomů a genomů rodin postižených dětí přispíváme k identifikaci dosud neznámých kauzálních genů, k upřesnění spekter mutací a fenotypů u genů popsaných zatím jen u malého počtu pacientů a k bližší charakterizaci genetických mechanismů těchto poruch. Věnujeme se pregraduální (bakalářské i magisterské obory) i postgraduální výuce studentů 2. LF UK.
Tým
Ph.D. studenti
Výzkumné projekty
Naše laboratoř je součástí Institucionální podpory excelentního výzkumu na 2. LF UK (IPE2): Molekulární charakterizace příčin závažných genetických onemocnění (6980364).
Granty
Probíhající granty
MZ, AZV NU22-07-00165, Identifikace a analýza genů a genových defektů způsobujících vzácné neurovývojové poruchy u dětí, 2022-2025
MŠMT, LM2018132, Národní centrum lékařské genomiky, 2020-2023
Ukončené granty
MZ, AZV 17-29423A, Analýza genetických variant asociovaných s mentální retardaci a poruchami autistického spektra s využitím sekvenování nové generace, 2017-2020
MŠMT, LM2015091, Národní centrum lékařské genomiky, 2016-2019
MZ, IGA NT14200, Identifikace genetických defektů v rodinách pacientů s autismem, 2013-2015
EU, TEMPUS MEDGEN - Developing Medical Genetics Education through Curriculum Reforms and Establishment of Postgraduate Training Programs, 2013-2017
COST, ESSEA - Enhancing the Scientific Study of Early Autism, BM1004/LD11028, 2011-2014
EU, CHERISH - Improving Diagnoses of Mental Retardation in Children in Central Eastern Europe and Central Asia through Genetic Characterisation and Bioinformatics/Statistics 7. RP EU 223692 FP7, 2009-2012
Ocenění
Čestné uznání ministra zdravotnictví v rámci Ceny ministra zdravotnictví za zdravotnický výzkum a vývoj pro rok 2021 grant AZV 17-29423A.
Publikace
2023
Vlckova M, Prchalova D, Zimmermann P, Haberlova J, Bendova S, Moslerova V, Stranecky V, Sedlacek Z, Hancarova M. A new patient with congenital myasthenic syndrome type 20 due to compound heterozygous missense SLC5A7 variants suggests trends in genotype-phenotype correlation. Mol Genet Genomic Med. 2023 Feb 24:e2154. doi: 10.1002/mgg3.2154.
2022
2021
Voisin N, Schnur RE, Douzgou S, Hiatt SM, Rustad CF, Brown NJ, Earl DL, Keren B, Levchenko O, Geuer S, Verheyen S, Johnson D, Zarate YA, Hančárová M, Amor DJ, Bebin EM, Blatterer J, Brusco A, Cappuccio G, Charrow J, Chatron N, Cooper GM, Courtin T, Dadali E, Delafontaine J, Del Giudice E, Doco M, Douglas G, Eisenkölbl A, Funari T, Giannuzzi G, Gruber-Sedlmayr U, Guex N, Heron D, Holla ØL, Hurst ACE, Juusola J, Kronn D, Lavrov A, Lee C, Lorrain S, Merckoll E, Mikhaleva A, Norman J, Pradervand S, Prchalová D, Rhodes L, Sanders VR, Sedláček Z, Seebacher HA, Sellars EA, Sirchia F, Takenouchi T, Tanaka AJ, Taska-Tench H, Tønne E, Tveten K, Vitiello G, Vlčková M, Uehara T, Nava C, Yalcin B, Kosaki K, Donnai D, Mundlos S, Brunetti-Pierri N, Chung WK, Reymond A. Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy. Am J Hum Genet. 2021 May 6;108(5):857-873. doi: 10.1016/j.ajhg.2021.04.001.
Jeanne M, Demory H, Moutal A, Vuillaume ML, Blesson S, Thépault RA, Marouillat S, Halewa J, Maas SM, Motazacker MM, Mancini GMS, van Slegtenhorst MA, Andreou A, Cox H, Vogt J, Laufman J, Kostandyan N, Babikyan D, Hancarova M, Bendova S, Sedlacek Z, Aldinger KA, Sherr EH, Argilli E, England EM, Audebert- Bellanger S, Bonneau D, Colin E, Denommé-Pichon AS, Gilbert-Dussardier B, Isidor B, Küry S, Odent S, Redon R, Khanna R, Dobyns WB, Bézieau S, Honnorat J, Lohkamp B, Toutain A, Laumonnier F. Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities. Am J Hum Genet. 2021 May 6;108(5):951-961. doi: 10.1016/j.ajhg.2021.04.004.
Chowdhury F, Wang L, Al-Raqad M, Amor DJ, Baxová A, Bendová Š, Biamino E, Brusco A, Caluseriu O, Cox NJ, Froukh T, Gunay-Aygun M, Hančárová M, Haynes D, Heide S, Hoganson G, Kaname T, Keren B, Kosaki K, Kubota K, Lemons JM, Magriña MA, Mark PR, McDonald MT, Montgomery S, Morley GM, Ohnishi H, Okamoto N, Rodriguez-Buritica D, Rump P, Sedláček Z, Schatz K, Streff H, Uehara T, Walia JS, Wheeler PG, Wiesener A, Zweier C, Kawakami K, Wentzensen IM, Lalani SR, Siu VM, Bi W, Balci TB. Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genet Med. 2021 Jul;23(7):1234-1245. doi: 10.1038/s41436-021-01129-6.
Sedláček, Zdeněk. Genetika neurovývojových poruch. Česká a slovenská psychiatrie. 2021, 117(2), 83-90. ISSN 1212-0383.
2020
Wang T, Hoekzema K, Vecchio D, Wu H, Sulovari A, Coe BP, Gillentine MA, Wilfert AB, Perez-Jurado LA, Kvarnung M, Sleyp Y, Earl RK, Rosenfeld JA, Geisheker MR, Han L, Du B, Barnett C, Thompson E, Shaw M, Carroll R, Friend K, Catford R, Palmer EE, Zou X, Ou J, Li H, Guo H, Gerdts J, Avola E, Calabrese G, Elia M, Greco D, Lindstrand A, Nordgren A, Anderlid BM, Vandeweyer G, Van Dijck A, Van der Aa N, McKenna B, Hancarova M, Bendova S, Havlovicova M, Malerba G, Bernardina BD, Muglia P, van Haeringen A, Hoffer MJV, Franke B, Cappuccio G, Delatycki M, Lockhart PJ, Manning MA, Liu P, Scheffer IE, Brunetti-Pierri N, Rommelse N, Amaral DG, Santen GWE, Trabetti E, Sedláček Z, Michaelson JJ, Pierce K, Courchesne E, Kooy RF; SPARK Consortium; Nordenskjöld M, Romano C, Peeters H, Bernier RA, Gecz J, Xia K, Eichler EE. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders. Nat Commun. 2020 Oct 1;11(1):4932. doi: 10.1038/s41467-020-18723-y. Erratum in: Nat Commun. 2020 Oct 21;11(1):5398. PMID: 33004838; PMCID: PMC7530681.
Cappuccio G, Sayou C, Tanno PL, Tisserant E, Bruel AL, Kennani SE, Sá J, Low KJ, Dias C, Havlovicová M, Hančárová M, Eichler EE, Devillard F, Moutton S, Van- Gils J, Dubourg C, Odent S, Gerard B, Piton A, Yamamoto T, Okamoto N, Firth H, Metcalfe K, Moh A, Chapman KA, Aref-Eshghi E, Kerkhof J, Torella A, Nigro V, Perrin L, Piard J, Le Guyader G, Jouan T, Thauvin-Robinet C, Duffourd Y, George- Abraham JK, Buchanan CA, Williams D, Kini U, Wilson K; Telethon Undiagnosed Diseases Program; Sousa SB, Hennekam RCM, Sadikovic B, Thevenon J, Govin J, Vitobello A, Brunetti-Pierri N. De novo SMARCA2 variants clustered outside the helicase domain cause a new recognizable syndrome with intellectual disability and blepharophimosis distinct from Nicolaides-Baraitser syndrome. Genet Med. 2020 Nov;22(11):1838-1850. doi: 10.1038/s41436-020-0898-y.
Necpál J, Zech M, Valachová A, Sedláček Z, Bendová Š, Hančárová M, Okáľová K, Winkelmann J, Jech R. Severe paroxysmal dyskinesias without epilepsy in a RHOBTB2 mutation carrier. Parkinsonism Relat Disord. 2020 Aug;77:87-88. doi: 10.1016/j.parkreldis.2020.06.028.
2019
Prochazkova K, Novotny P, Hancarova M, Prchalova D, Sedlacek Z. Teaching a difficult topic using a problem-based concept resembling a computer game: development and evaluation of an e-learning application for medical molecular genetics. BMC Med Educ. 2019 Oct 24;19(1):390. doi: 10.1186/s12909-019-1817-2.
Fiordaliso SK, Iwata-Otsubo A, Ritter AL, Quesnel-Vallières M, Fujiki K, Nishi E, Hancarova M, Miyake N, Morton JEV, Lee S, Hackmann K, Bando M, Masuda K, Nakato R, Arakawa M, Bhoj E, Li D, Hakonarson H, Takeda R, Harr M, Keena B, Zackai EH, Okamoto N, Mizuno S, Ko JM, Valachova A, Prchalova D, Vlckova M, Pippucci T, Seiler C, Choi M, Matsumoto N, Di Donato N, Barash Y, Sedlacek Z, Shirahige K, Izumi K. Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment. Am J Hum Genet. 2019 Nov 7;105(5):987-995. doi: 10.1016/j.ajhg.2019.09.009.
Hancarova M, Havlovicova M, Putzova M, Vseticka J, Prchalova D, Stranecky V, Sedlacek Z. Parental gonadal but not somatic mosaicism leading to de novo NFIX variants shared by two brothers with Malan syndrome. Am J Med Genet A. 2019 Oct;179(10):2119-2123. doi: 10.1002/ajmg.a.61302.
Haijes HA, Koster MJE, Rehmann H, Li D, Hakonarson H, Cappuccio G, Hancarova M, Lehalle D, Reardon W, Schaefer GB, Lehman A, van de Laar IMBH, Tesselaar CD, Turner C, Goldenberg A, Patrier S, Thevenon J, Pinelli M, Brunetti-Pierri N, Prchalová D, Havlovicová M, Vlckova M, Sedláček Z, Lopez E, Ragoussis V, Pagnamenta AT, Kini U, Vos HR, van Es RM, van Schaik RFMA, van Essen TAJ, Kibaek M, Taylor JC, Sullivan J, Shashi V, Petrovski S, Fagerberg C, Martin DM, van Gassen KLI, Pfundt R, Falk MJ, McCormick EM, Timmers HTM, van Hasselt PM. De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia. Am J Hum Genet. 2019 Aug 1;105(2):283-301. doi: 10.1016/j.ajhg.2019.06.016.
Hancarova M, Babikyan D, Bendova S, Midyan S, Prchalova D, Shahsuvaryan G, Stranecky V, Sarkisian T, Sedlacek Z. A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype. Mol Genet Genomic Med. 2019 Sep;7(9):e865. doi: 10.1002/mgg3.865.
2018
Hiatt SM, Neu MB, Ramaker RC, Hardigan AA, Prokop JW, Hancarova M, Prchalova D, Havlovicova M, Prchal J, Stranecky V, Yim DKC, Powis Z, Keren B, Nava C, Mignot C, Rio M, Revah-Politi A, Hemati P, Stong N, Iglesias AD, Suchy SF, Willaert R, Wentzensen IM, Wheeler PG, Brick L, Kozenko M, Hurst ACE, Wheless JW, Lacassie Y, Myers RM, Barsh GS, Sedlacek Z, Cooper GM. De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay. PLoS Genet. 2018 Nov 30;14(11):e1007671. doi: 10.1371/journal.pgen.1007671.
Mignot C, McMahon AC, Bar C, Campeau PM, Davidson C, Buratti J, Nava C, Jacquemont ML, Tallot M, Milh M, Edery P, Marzin P, Barcia G, Barnerias C, Besmond C, Bienvenu T, Bruel AL, Brunga L, Ceulemans B, Coubes C, Cristancho AG, Cunningham F, Dehouck MB, Donner EJ, Duban-Bedu B, Dubourg C, Gardella E, Gauthier J, Geneviève D, Gobin-Limballe S, Goldberg EM, Hagebeuk E, Hamdan FF, Hančárová M, Hubert L, Ioos C, Ichikawa S, Janssens S, Journel H, Kaminska A, Keren B, Koopmans M, Lacoste C, Laššuthová P, Lederer D, Lehalle D, Marjanovic D, Métreau J, Michaud JL, Miller K, Minassian BA, Morales J, Moutard ML, Munnich A, Ortiz-Gonzalez XR, Pinard JM, Prchalová D, Putoux A, Quelin C, Rosen AR, Roume J, Rossignol E, Simon MEH, Smol T, Shur N, Shelihan I, Štěrbová K, Vyhnálková E, Vilain C, Soblet J, Smits G, Yang SP, van der Smagt JJ, van Hasselt PM, van Kempen M, Weckhuysen S, Helbig I, Villard L, Héron D, Koeleman B, Møller RS, Lesca G, Helbig KL, Nabbout R, Verbeek NE, Depienne C. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients. Genet Med. 2019 Apr;21(4):837-849. doi: 10.1038/s41436-018-0268-1.
Tesner P, Vlckova M, Drabova J, Vseticka J, Klimova A, Lastuvkova J, Zidovska J, Kremlikova Pourova R, Hancarova M, Sedlacek Z, Kocarek E. Molecular Cytogenetic Diagnostics of Marker Chromosomes: Analysis in Four Prenatal Cases and Long-Term Clinical Evaluation of Carriers. Cytogenet Genome Res. 2018;154(4):187-195. doi: 10.1159/000488790.
Hancarova M, Malikova M, Kotrova M, Drabova J, Trkova M, Sedlacek Z. Association of 17q24.2-q24.3 deletions with recognizable phenotype and short telomeres. Am J Med Genet A. 2018 Jun;176(6):1438-1442. doi: 10.1002/ajmg.a.38711.
Tesner P, Drabova J, Stolfa M, Kudr M, Kyncl M, Moslerova V, Novotna D, Kremlikova Pourova R, Kocarek E, Rasplickova T, Sedlacek Z, Vlckova M. A boy with developmental delay and mosaic supernumerary inv dup(5)(p15.33p15.1) leading to distal 5p tetrasomy - case report and review of the literature. Mol Cytogenet. 2018 May 9;11:29. doi: 10.1186/s13039-018-0377-1.
Slamova Z, Nazaryan-Petersen L, Mehrjouy MM, Drabova J, Hancarova M, Marikova T, Novotna D, Vlckova M, Vlckova Z, Bak M, Zemanova Z, Tommerup N, Sedlacek Z. Very short DNA segments can be detected and handled by the repair machinery during germline chromothriptic chromosome reassembly. Hum Mutat. 2018 May;39(5):709-716. doi: 10.1002/humu.23408.
2017
Barbé L, Lanni S, López-Castel A, Franck S, Spits C, Keymolen K, Seneca S, Tomé S, Miron I, Letourneau J, Liang M, Choufani S, Weksberg R, Wilson MD, Sedlacek Z, Gagnon C, Musova Z, Chitayat D, Shannon P, Mathieu J, Sermon K, Pearson CE. CpG Methylation, a Parent-of-Origin Effect for Maternal-Biased Transmission of Congenital Myotonic Dystrophy. Am J Hum Genet. 2017 Mar 2;100(3):488-505. doi: 10.1016/j.ajhg.2017.01.033.
Geisheker MR, Heymann G, Wang T, Coe BP, Turner TN, Stessman HAF, Hoekzema K, Kvarnung M, Shaw M, Friend K, Liebelt J, Barnett C, Thompson EM, Haan E, Guo H, Anderlid BM, Nordgren A, Lindstrand A, Vandeweyer G, Alberti A, Avola E, Vinci M, Giusto S, Pramparo T, Pierce K, Nalabolu S, Michaelson JJ, Sedlacek Z, Santen GWE, Peeters H, Hakonarson H, Courchesne E, Romano C, Kooy RF, Bernier RA, Nordenskjöld M, Gecz J, Xia K, Zweifel LS, Eichler EE. Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains. Nat Neurosci. 2017 Aug;20(8):1043-1051. doi: 10.1038/nn.4589.
Meerschaut I, Rochefort D, Revençu N, Pètre J, Corsello C, Rouleau GA, Hamdan FF, Michaud JL, Morton J, Radley J, Ragge N, García-Miñaúr S, Lapunzina P, Bralo MP, Mori MÁ, Moortgat S, Benoit V, Mary S, Bockaert N, Oostra A, Vanakker O, Velinov M, de Ravel TJ, Mekahli D, Sebat J, Vaux KK, DiDonato N, Hanson-Kahn AK, Hudgins L, Dallapiccola B, Novelli A, Tarani L, Andrieux J, Parker MJ, Neas K, Ceulemans B, Schoonjans AS, Prchalova D, Havlovicova M, Hancarova M, Budisteanu M, Dheedene A, Menten B, Dion PA, Lederer D, Callewaert B. FOXP1-related intellectual disability syndrome: a recognisable entity. J Med Genet. 2017 Sep;54(9):613-623. doi: 10.1136/jmedgenet-2017-104579.
Prchalova D, Havlovicova M, Sterbova K, Stranecky V, Hancarova M, Sedlacek Z. Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report. BMC Med Genet. 2017 Jun 2;18(1):62. doi: 10.1186/s12881-017-0425-4.
2016
El Chehadeh S, Kerstjens-Frederikse WS, Thevenon J, Kuentz P, Bruel AL, Thauvin-Robinet C, Bensignor C, Dollfus H, Laugel V, Rivière JB, Duffourd Y, Bonnet C, Robert MP, Isaiko R, Straub M, Creuzot-Garcher C, Calvas P, Chassaing N, Loeys B, Reyniers E, Vandeweyer G, Kooy F, Hančárová M, Havlovicová M, Prchalová D, Sedláček Z, Gilissen C, Pfundt R, Wassink-Ruiter JSK, Faivre L. Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature. Eur J Hum Genet. 2016 Jan;25(1):43-51. doi: 10.1038/ejhg.2016.133.
Musova Z, Hancarova M, Havlovicova M, Pourova R, Hrdlicka M, Kraus J, Trkova M, Stejskal D, Sedlacek Z. Expanded DMPK repeats in dizygotic twins referred for diagnosis of autism versus absence of expanded DMPK repeats at screening of 330 children with autism. Neuropsychiatr Dis Treat. 2016 Sep 19;12:2367-2372. doi: 10.2147/NDT.S113917.
2015
Vlckova M, Simandlova M, Zimmermann P, Stranecky V, Hartmannova H, Hodanova K, Havlovicova M, Hancarova M, Kmoch S, Sedlacek Z. A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes. Eur J Med Genet. 2015 Oct;58(10):550-5. doi: 10.1016/j.ejmg.2015.09.004.
Basak A, Hancarova M, Ulirsch JC, Balci TB, Trkova M, Pelisek M, Vlckova M, Muzikova K, Cermak J, Trka J, Dyment DA, Orkin SH, Daly MJ, Sedlacek Z, Sankaran VG. BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations. J Clin Invest. 2015 Jun;125(6):2363-8. doi: 10.1172/JCI81163.
Hancarova M, Krepelova A, Puchmajerova A, Soucek O, Prchalova D, Sumnik Z, Sedlacek Z. Hypophosphatasia due to uniparental disomy. Bone. 2015 Dec;81:765-766. doi: 10.1016/j.bone.2015.04.041.
Jolly LA, Nguyen LS, Domingo D, Sun Y, Barry S, Hancarova M, Plevova P, Vlckova M, Havlovicova M, Kalscheuer VM, Graziano C, Pippucci T, Bonora E, Sedlacek Z, Gecz J. HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain. Hum Mol Genet. 2015 Jun 15;24(12):3335-47. doi: 10.1093/hmg/ddv083.
Drabova J, Seemanova E, Hancarova M, Pourova R, Horacek M, Jancuskova T, Pekova S, Novotna D, Sedlacek Z. Long term follow-up in a patient with a de novo microdeletion of 14q11.2 involving CHD8. Am J Med Genet A. 2015 Apr;167A(4):837-41. doi: 10.1002/ajmg.a.36957.
2014
Drabova J, Trkova M, Hancarova M, Novotna D, Hejtmankova M, Havlovicova M, Sedlacek Z. A 15 Mb large paracentric chromosome 21 inversion identified in Czech population through a pair of flanking duplications. Mol Cytogenet. 2014 Aug 19;7:51. doi: 10.1186/1755-8166-7-51.
Hancarova M, Puchmajerova A, Drabova J, Karaskova E, Vlckova M, Sedlacek Z. Deletions of 9q21.3 including NTRK2 are associated with severe phenotype. Am J Med Genet A. 2015 Jan;167A(1):264-7. doi: 10.1002/ajmg.a.36797.
Vlckova M, Hancarova M, Drabova J, Slamova Z, Koudova M, Alanova R, Mannik K, Kurg A, Sedlacek Z. Monozygotic twins with 17q21.31 microdeletion syndrome. Twin Res Hum Genet. 2014 Oct;17(5):405-10. doi: 10.1017/thg.2014.29.
2013
Hancarova M, Simandlova M, Drabova J, Mannik K, Kurg A, Sedlacek Z. A patient with de novo 0.45 Mb deletion of 2p16.1: the role of BCL11A, PAPOLG, REL, and FLJ16341 in the 2p15-p16.1 microdeletion syndrome. Am J Med Genet A. 2013 Apr;161A(4):865-70. doi: 10.1002/ajmg.a.35783.
Hancarova M, Simandlova M, Drabova J, Petrak B, Koudova M, Havlovicova M, Sedlacek Z. Chromosome 12q13.13 deletions involving the HOXC gene cluster: phenotype and candidate genes. Eur J Med Genet. 2013 Mar;56(3):171-3. doi: 10.1016/j.ejmg.2012.12.003.
Hancarova M, Vejvalkova S, Trkova M, Drabova J, Dleskova A, Vlckova M, Sedlacek Z. Identification of a patient with intellectual disability and de novo 3.7 Mb deletion supports the existence of a novel microdeletion syndrome in 2p14-p15. Gene. 2013 Mar 1;516(1):158-61. doi: 10.1016/j.gene.2012.12.027.
