Publications 2015

TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function. Ba W, Yan Y, Reijnders MR, Schuurs-Hoeijmakers JH, Feenstra I, Bongers EM, Bosch DG, De Leeuw N, Pfundt R, Gilissen C, De Vries PF, Veltman JA, Hoischen A, Mefford HC, Eichler EE, Vissers LE, Nadif Kasri N, De Vries BB
Hum Mol Genet. 2015 Dec 31. pii: ddv618. [Epub ahead of print]


Influence of paternal age on ongoing pregnancy rate at eight weeks' gestation in assisted reproduction. Meijerink AM, Ramos L, Fleischer K, Veltman JA, Hendriks JC, Braat DD
Reprod Biomed Online. 2016 Jan;32(1):96-103. doi: 10.1016/j.rbmo.2015.09.017. Epub 2015 Oct 22


Standardized phenotyping enhances Mendelian disease gene identification. Vissers LE, Veltman JA.
Nat Genet. 2015 Oct 28;47(11):1222-4. doi: 10.1038/ng.3425.


Genetic studies in intellectual disability and related disorders. Vissers LE, Gilissen C, Veltman JA.
Nat Rev Genet. 2016 Jan;17(1):9-18. doi: 10.1038/nrg3999. Epub 2015 Oct 27.


Cell-Free RNA Is a Reliable Fetoplacental Marker in Noninvasive Fetal Sex Determination. Mersy E, Faas BH, Spierts S, Houben LM, Macville MV, Frints SG, Paulussen AD, Veltman JA.
Clin Chem. 2015 Oct 14. pii: clinchem.2015.244962. [Epub ahead of print


Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects. Vrijenhoek T, Kraaijeveld K, Elferink M, de Ligt J, Kranendonk E, Santen G, Nijman IJ, Butler D, Claes G, Costessi A, Dorlijn W, van Eyndhoven W, Halley DJ, van den Hout MC, van Hove S, Johansson LF, Jongbloed JD, Kamps R, Kockx CE, de Koning B, Kriek M, Deprez RL, Lunstroo H, Mannens M, Mook OR, Nelen M, Ploem C, Rijnen M, Saris JJ, Sinke R, Sistermans E, van Slegtenhorst M, Sleutels F, van der Stoep N, van Tienhoven M, Vermaat M, Vogel M, Waisfisz Q, Weiss JM, van den Wijngaard A, van Workum W, Ijntema H, van der Zwaag B, van IJcken WF, den Dunnen JT, Veltman JA, Hennekam R, Cuppen E.
Eur J Hum Genet. 2015 Sep;23(9):1270. doi: 10.1038/ejhg.2015.44. No abstract available.


Novel genetic causes for cerebral visual impairment. Bosch DG, Boonstra FN, de Leeuw N, Pfundt R, Nillesen WM, de Ligt J, Gilissen C, Jhangiani S, Lupski JR, Cremers FP, de Vries BB.
Eur J Hum Genet. 2015 Sep 9. doi: 10.1038/ejhg.2015.186. [Epub ahead of print]


Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer. de Voer RM, Hahn MM, Mensenkamp AR, Hoischen A, Gilissen C, Henkes A, Spruijt L, van Zelst-Stams WA, Marleen Kets C, Verwiel ET, Nagtegaal ID, Schackert HK, van Kessel AG, Hoogerbrugge N, Ligtenberg MJ, Kuiper RP.
Sci Rep. 2015 Sep 11;5:14060. doi: 10.1038/srep14060.


The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.Koolen DA, Pfundt R, Linda K, Beunders G, Veenstra-Knol HE, Conta JH, Fortuna AM, Gillessen-Kaesbach G, Dugan S, Halbach S, Abdul-Rahman OA, Winesett HM, Chung WK, Dalton M, Dimova PS, Mattina T, Prescott K, Zhang HZ, Saal HM, Hehir-Kwa JY, Willemsen MH, Ockeloen CW, Jongmans MC, Van der Aa N, Failla P, Barone C, Avola E, Brooks AS, Kant SG, Gerkes EH, Firth HV, Õunap K, Bird LM, Masser-Frye D, Friedman JR, Sokunbi MA, Dixit A, Splitt M; DDD Study, Kukolich MK, McGaughran J, Coe BP, Flórez J, Nadif Kasri N, Brunner HG, Thompson EM, Gecz J, Romano C, Eichler EE, de Vries BB.
Eur J Hum Genet. 2015 Aug 26. doi: 10.1038/ejhg.2015.178. [Epub ahead of print]


Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling. Snijders Blok L, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MR, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LE, Koemans TS, Wissink-Lindhout W, Eichler EE, Romano C, Van Esch H, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BW, Shaw M, Gecz J, Haan E, Bienek M, Jensen C, Loeys BL, Van Dijck A, Innes AM, Racher H, Vermeer S, Di Donato N, Rump A, Tatton-Brown K, Parker MJ, Henderson A, Lynch SA, Fryer A, Ross A, Vasudevan P, Kini U, Newbury-Ecob R, Chandler K, Male A; DDD Study, Dijkstra S, Schieving J, Giltay J, van Gassen KL, Schuurs-Hoeijmakers J, Tan PL, Pediaditakis I, Haas SA, Retterer K, Reed P, Monaghan KG, Haverfield E, Natowicz M, Myers A, Kruer MC, Stein Q, Strauss KA, Brigatti KW, Keating K, Burton BK, Kim KH, Charrow J, Norman J, Foster-Barber A, Kline AD, Kimball A, Zackai E, Harr M, Fox J, McLaughlin J, Lindstrom K, Haude KM, van Roozendaal K, Brunner H, Chung WK, Kooy RF, Pfundt R, Kalscheuer V, Mehta SG, Katsanis N, Kleefstra T
Am J Hum Genet. 2015 Aug 6;97(2):343-52. doi: 10.1016/j.ajhg.2015.07.004. Epub 2015 Jul 30.


The heat shock response restricts virus infection in Drosophila. Merkling SH, Overheul GJ, van Mierlo JT, Arends D, Gilissen C, van Rij RP.
Sci Rep. 2015 Aug 3;5:12758. doi: 10.1038/srep12758.


From genes to genomes in the clinic. Veltman JA, Lupski JR.
Genome Med. 2015 Jul 29;7(1):78. doi: 10.1186/s13073-015-0200-0. eCollection 2015.


Independent development of lymphoid and histiocytic malignancies from a shared early precursor. Waanders E, Hebeda KM, Kamping EJ, Groenen PJ, Simons A, Hoischen A, Jongmans MC, Hoogerbrugge PM, van Leeuwen FN, Kuiper RP, Te Loo DM.
Leukemia. 2015 Jul 23. doi: 10.1038/leu.2015.193. [Epub ahead of print] No abstract available.


Advantages and Disadvantages of Different Implementation Strategies of Non-Invasive Prenatal Testing in Down Syndrome Screening Programmes. Mersy E, de Die-Smulders CE, Coumans AB, Smits LJ, de Wert GM, Frints SG, Veltman JA.
Public Health Genomics. 2015 Jul 18. [Epub ahead of print]


Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration. Iqbal Z, Püttmann L, Musante L, Razzaq A, Zahoor MY, Hu H, Wienker TF, Garshasbi M, Fattahi Z, Gilissen C, Vissers LE, de Brouwer AP, Veltman JA, Pfundt R, Najmabadi H, Ropers HH, Riazuddin S, Kahrizi K, van Bokhoven H.
Eur J Hum Genet. 2015 Jul 15. doi: 10.1038/ejhg.2015.148. [Epub ahead of print]


B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability. Houge G, Haesen D, Vissers LE, Mehta S, Parker MJ, Wright M, Vogt J, McKee S, Tolmie JL, Cordeiro N, Kleefstra T, Willemsen MH, Reijnders MR, Berland S, Hayman E, Lahat E, Brilstra EH, van Gassen KL, Zonneveld-Huijssoon E, de Bie CI, Hoischen A, Eichler EE, Holdhus R, Steen VM, Døskeland SO, Hurles ME, FitzPatrick DR, Janssens V.
J Clin Invest. 2015 Aug 3;125(8):3051-62. doi: 10.1172/JCI79860. Epub 2015 Jul 13.


Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes. Marchegiani S, Davis T, Tessadori F, van Haaften G, Brancati F, Hoischen A, Huang H, Valkanas E, Pusey B, Schanze D, Venselaar H, Vulto-van Silfhout AT, Wolfe LA, Tifft CJ, Zerfas PM, Zambruno G, Kariminejad A, Sabbagh-Kermani F, Lee J, Tsokos MG, Lee CC, Ferraz V, da Silva EM, Stevens CA, Roche N, Bartsch O, Farndon P, Bermejo-Sanchez E, Brooks BP, Maduro V, Dallapiccola B, Ramos FJ, Chung HY, Le Caignec C, Martins F, Jacyk WK, Mazzanti L, Brunner HG, Bakkers J, Lin S, Malicdan MC, Boerkoel CF, Gahl WA, de Vries BB, van Haelst MM, Zenker M, Markello TC.
Am J Hum Genet. 2015 Jul 2;97(1):99-110. doi: 10.1016/j.ajhg.2015.05.017. Epub 2015 Jun 25.


Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi. Chipungu C, Veltman JA, Jansen P, Chiliko P, Lossa C, Namarika D, Benner B, Hoffman RM, Bristow CC, Klausner JD.
J Int Assoc Provid AIDS Care. 2015 Jul 2. pii: 2325957415592475. [Epub ahead of print]


Exome sequencing and whole genome sequencing for the detection of copy number variation. Hehir-Kwa JY, Pfundt R, Veltman JA.
Expert Rev Mol Diagn. 2015 Aug;15(8):1023-32. doi: 10.1586/14737159.2015.1053467. Epub 2015 Jun 18.


Post-zygotic Point Mutations Are an Underrecognized Source of De Novo Genomic Variation Acuna-Hidalgo R, Bo T, Kwint MP, van de Vorst M, Pinelli M, Veltman JA, Hoischen A, Vissers LE, Gilissen C.
Am J Hum Genet. 2015 Jul 2;97(1):67-74. doi: 10.1016/j.ajhg.2015.05.008. Epub 2015 Jun 6


Comparison of Exome and Genome Sequencing Technologies for the Complete Capture of Protein-Coding Regions. Lelieveld SH, Spielmann M, Mundlos S, Veltman JA, Gilissen C.
Hum Mutat. 2015 Aug;36(8):815-22. doi: 10.1002/humu.22813. Epub 2015 Jun 11


De novo mutations in PLXND1 and REV3L cause Möbius syndrome. Tomas-Roca L, Tsaalbi-Shtylik A, Jansen JG, Singh MK, Epstein JA, Altunoglu U, Verzijl H, Soria L, van Beusekom E, Roscioli T, Iqbal Z, Gilissen C, Hoischen A, de Brouwer AP, Erasmus C, Schubert D, Brunner H, Pérez Aytés A, Marin F, Aroca P, Kayserili H, Carta A, de Wind N, Padberg GW, van Bokhoven H.
Nat Commun. 2015 Jun 12;6:7199. doi: 10.1038/ncomms8199.


Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease. Pottier C, Bieniek KF, Finch N, van de Vorst M, Baker M, Perkersen R, Brown P, Ravenscroft T, van Blitterswijk M, Nicholson AM, DeTure M, Knopman DS, Josephs KA, Parisi JE, Petersen RC, Boylan KB, Boeve BF, Graff-Radford NR, Veltman JA, Gilissen C, Murray ME, Dickson DW, Rademakers R.
Acta Neuropathol. 2015 Jul;130(1):77-92. doi: 10.1007/s00401-015-1436-x. Epub 2015 May 6.


A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Weren RD, Ligtenberg MJ, Kets CM, de Voer RM, Verwiel ET, Spruijt L, van Zelst-Stams WA, Jongmans MC, Gilissen C, Hehir-Kwa JY, Hoischen A, Shendure J, Boyle EA, Kamping EJ, Nagtegaal ID, Tops BB, Nagengast FM, Geurts van Kessel A, van Krieken JH, Kuiper RP, Hoogerbrugge N.
Nat Genet. 2015 Jun;47(6):668-71. doi: 10.1038/ng.3287. Epub 2015 May 4.


LRP5 variants may contribute to ADPKD. Cnossen WR, Te Morsche RH, Hoischen A, Gilissen C, Venselaar H, Mehdi S, Bergmann C, Losekoot M, Breuning MH, Peters DJ, Veltman JA, Drenth JP.
Eur J Hum Genet. 2015 Apr 29. doi: 10.1038/ejhg.2015.86. [Epub ahead of print]


Evaluating a counselling strategy for diagnostic WES in paediatric neurology: an exploration of parents' information and communication needs. Krabbenborg L, Schieving J, Kleefstra T, Vissers LE, Willemsen MA, Veltman JA, van der Burg
Clin Genet. 2015 Apr 28. doi: 10.1111/cge.12601. [Epub ahead of print]


A recent bottleneck of Y chromosome diversity coincides with a global change in culture. Karmin M, Saag L, Vicente M, Wilson Sayres MA, Järve M, Talas UG, Rootsi S, Ilumäe AM, Mägi R, Mitt M, Pagani L, Puurand T, Faltyskova Z, Clemente F, Cardona A, Metspalu E, Sahakyan H, Yunusbayev B, Hudjashov G, DeGiorgio M, Loogväli EL, Eichstaedt C, Eelmets M, Chaubey G, Tambets K, Litvinov S, Mormina M, Xue Y, Ayub Q, Zoraqi G, Korneliussen TS, Akhatova F, Lachance J, Tishkoff S, Momynaliev K, Ricaut FX, Kusuma P, Razafindrazaka H, Pierron D, Cox MP, Sultana GN, Willerslev R, Muller C, Westaway M, Lambert D, Skaro V, Kovačevic L, Turdikulova S, Dalimova D, Khusainova R, Trofimova N, Akhmetova V, Khidiyatova I, Lichman DV, Isakova J, Pocheshkhova E, Sabitov Z, Barashkov NA, Nymadawa P, Mihailov E, Seng JW, Evseeva I, Migliano AB, Abdullah S, Andriadze G, Primorac D, Atramentova L, Utevska O, Yepiskoposyan L, Marjanovic D, Kushniarevich A, Behar DM, Gilissen C, Vissers L, Veltman JA, Balanovska E, Derenko M, Malyarchuk B, Metspalu A, Fedorova S, Eriksson A, Manica A, Mendez FL, Karafet TM, Veeramah KR, Bradman N, Hammer MF, Osipova LP, Balanovsky O, Khusnutdinova EK, Johnsen K, Remm M, Thomas MG, Tyler-Smith C, Underhill PA, Willerslev E, Nielsen R, Metspalu M, Villems R, Kivisild T.
Genome Res. 2015 Apr;25(4):459-66. doi: 10.1101/gr.186684.114. Epub 2015 Mar 13


Immunoglobulin rearrangement analysis from multiple lesions in the same patient using Next Generation Sequencing. Appenzeller S, Gilissen C, Rijntjes J, Tops BB, Kastner-van Raaij A, Hebeda KM, Nissen L, Dutilh BE, van Krieken JH, Groenen PJ.
Histopathology. 2015 Apr 18. doi: 10.1111/his.12714. [Epub ahead of print]


Clustering of functionally-related genes impacts significantly on CNV-mediated disease Andrews T, Honti F, Pfundt R, de Leeuw N, Hehir-Kwa J, Vulto-van Silfout A, de Vries B, Webber C.
Genome Res. 2015 Apr 17. pii: gr.184325.114. [Epub ahead of print]


DVL1 Frameshift Mutations Clustering in the Penultimate Exon Cause Autosomal-Dominant Robinow Syndrome. White J, Mazzeu JF, Hoischen A, Jhangiani SN, Gambin T, Alcino MC, Penney S, Saraiva JM, Hove H, Skovby F, Kayserili H, Estrella E, Vulto-van Silfhout AT, Steehouwer M, Muzny DM, Sutton VR, Gibbs RA; Baylor-Hopkins Center for Mendelian Genomics, Lupski JR, Brunner HG, van Bon BW, Carvalho CM.
Am J Hum Genet. 2015 Apr 2;96(4):612-22. doi: 10.1016/j.ajhg.2015.02.015. Epub 2015 Mar 26.


Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders. Andrews T, Meader S, Vulto-van Silfhout A, Taylor A, Steinberg J, Hehir-Kwa J, Pfundt R, de Leeuw N, de Vries BB, Webber C.
PLoS Genet. 2015 Mar 17;11(3):e1005012. doi: 10.1371/journal.pgen.1005012. eCollection 2015 Mar


Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment Villanueva P, Nudel R, Hoischen A, Fernández MA, Simpson NH, Gilissen C, Reader RH, Jara L, Echeverry MM, Francks C, Baird G, Conti-Ramsden G, O'Hare A, Bolton PF, Hennessy ER; SLI Consortium, Palomino H, Carvajal-Carmona L, Veltman JA, Cazier JB, De Barbieri Z, Fisher SE, Newbury DF
PLoS Genet. 2015 Mar 17;11(3):e1004925. doi: 10.1371/journal.pgen.1004925. eCollection 2015 Mar


Homozygous SLC6A17 mutations cause autosomal-recessive intellectual disability with progressive tremor, speech impairment, and behavioral problems. Iqbal Z, Willemsen MH, Papon MA, Musante L, Benevento M, Hu H, Venselaar H, Wissink-Lindhout WM, Vulto-van Silfhout AT, Vissers LE, de Brouwer AP, Marouillat S, Wienker TF, Ropers HH, Kahrizi K, Nadif Kasri N, Najmabadi H, Laumonnier F, Kleefstra T, van Bokhoven H.
Am J Hum Genet. 2015 Mar 5;96(3):386-96. doi: 10.1016/j.ajhg.2015.01.010. Epub 2015 Feb 19.


Syndromic X-linked intellectual disability segregating with a missense variant in RLIM. Tønne E, Holdhus R, Stansberg C, Stray-Pedersen A, Petersen K, Brunner HG, Gilissen C, Hoischen A, Prescott T, Steen VM, Fiskerstrand T.
Eur J Hum Genet. 2015 Mar 4. doi: 10.1038/ejhg.2015.30. [Epub ahead of print]


Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA). Tylki-Szymańska A, Acuna-Hidalgo R, Krajewska-Walasek M, Lecka-Ambroziak A, Steehouwer M, Gilissen C, Brunner HG, Jurecka A, Różdżyńska-Świątkowska A, Hoischen A, Chrzanowska KH.
J Med Genet. 2015 May;52(5):312-6. doi: 10.1136/jmedgenet-2014-102936. Epub 2015 Feb 10


A missense mutation underlies defective SOCS4 function in a family with autoimmunity Arts P, Plantinga TS, van den Berg JM, Gilissen C, Veltman JA, van Trotsenburg AS, van de Veerdonk FL, Kuijpers TW, Hoischen A, Netea MG.
J Intern Med. 2015 Jan 31. doi: 10.1111/joim.12351. [Epub ahead of print]


Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects Vrijenhoek T, Kraaijeveld K, Elferink M, de Ligt J, Kranendonk E, Santen G, Nijman IJ, Butler D, Claes G, Costessi A, Dorlijn W, van Eyndhoven W, Halley DJ, van den Hout MC, van Hove S, Johansson LF, Jongbloed JD, Kamps R, Kockx CE, de Koning B, Kriek M, Lekanne Dit Deprez R, Lunstroo H, Mannens M, Nelen M, Ploem C, Rijnen M, Saris JJ, Sinke R, Sistermans E, van Slegtenhorst M, Sleutels F, van der Stoep N, van Tienhoven M, Vermaat M, Vogel M, Waisfisz Q, Marjan Weiss J, van den Wijngaard A, van Workum W, Ijntema H, van der Zwaag B, van IJcken WF, den Dunnen J, Veltman JA, Hennekam R, Cuppen E.
Eur J Hum Genet. 2015 Jan 28. doi: 10.1038/ejhg.2014.279. [Epub ahead of print]


Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency Van Scherpenzeel M, Timal S, Rymen D, Hoischen A, Wuhrer M, Hipgrave-Ederveen A, Grunewald S, Peanne R, Saada A, Edvardson S, Grønborg S, Ruijter G, Kattentidt-Mouravieva A, Brum JM, Freckmann ML, Tomkins S, Jalan A, Prochazkova D, Ondruskova N, Hansikova H, Willemsen MA, Hensbergen PJ, Matthijs G, Wevers RA, Veltman JA, Morava E, Lefeber DJ
Hum Mutat. 2015 Jan;36(1):106-17. doi: 10.1002/humu.22718


Clinical exome sequencing in daily practice: 1,000 patients and beyond van Zelst-Stams WA, Scheffer H, Veltman JA.
Genome Med. 2014 Jan 24;6(1):2. doi: 10.1186/gm521. eCollection 2014. No abstract available


Variants in CUL4B are Associated with Cerebral Malformations Vulto-van Silfhout AT1, Nakagawa T, Bahi-Buisson N, Haas SA, Hu H, Bienek M, Vissers LE, Gilissen C, Tzschach A, Busche A, Müsebeck J, Rump P, Mathijssen IB, Avela K, Somer M, Doagu F, Philips AK, Rauch A, Baumer A, Voesenek K, Poirier K, Vigneron J, Amram D, Odent S, Nawara M, Obersztyn E, Lenart J, Charzewska A, Lebrun N, Fischer U, Nillesen WM, Yntema HG, Järvelä I, Ropers HH, de Vries BB, Brunner HG, van Bokhoven H, Raymond FL, Willemsen MA, Chelly J, Xiong Y, Barkovich AJ, Kalscheuer VM, Kleefstra T, de Brouwer AP
Hum Mutat. 2015 Jan;36(1):106-17. doi: 10.1002/humu.22718

Reply to Sajantila and Budowle Barton DE1, Claustres M2, Kozich V3, Dequeker E4, Fowler B5, Hehir-Kwa JY6, Miller K7, Oosterwijk C8, Peterlin B9, van Ravenswaaij-Arts C10, Zimmermann U11, Zuffardi O12, Hastings RJ13.
Eur J Hum Genet. 2015 Jan 14. doi: 10.1038/ejhg.2014.290. [Epub ahead of print]