1. MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study
- Author
-
Makrythanasis, P, van Bon, BW, Steehouwer, M, Rodríguez-Santiago, B, Simpson, M, Dias, P, Anderlid, BM, Arts, P, Bhat, M, Augello, B, Biamino, E, Bongers, EMHF, del Campo, M, Cordeiro, I, Cueto-González, AM, Cuscó, I, Deshpande, C, Frysira, E, Izatt, L, Flores, R, Galán, E, Gener, B, Gilissen, C, Granneman, SM, Hoyer, J, Yntema, HG, Kets, CM, Koolen, DA, Marcelis, CL, Medeira, A, Micale, L, Mohammed, S, de Munnik, SA, Nordgren, A, Psoni, S, Reardon, W, Revencu, N, Roscioli, T, Ruiterkamp-Versteeg, M, Santos, HG, Schoumans, J, Schuurs-Hoeijmakers, JHM, Silengo, MC, Toledo, L, Vendrell, T, van der Burgt, I, van Lier, B, Zweier, C, Reymond, A, Trembath, RC, Perez-Jurado, L, Dupont, J, de Vries, BBA, Brunner, HG, Veltman, JA, Merla, G, Antonarakis, SE, Hoischen, A, Makrythanasis, P, van Bon, BW, Steehouwer, M, Rodríguez-Santiago, B, Simpson, M, Dias, P, Anderlid, BM, Arts, P, Bhat, M, Augello, B, Biamino, E, Bongers, EMHF, del Campo, M, Cordeiro, I, Cueto-González, AM, Cuscó, I, Deshpande, C, Frysira, E, Izatt, L, Flores, R, Galán, E, Gener, B, Gilissen, C, Granneman, SM, Hoyer, J, Yntema, HG, Kets, CM, Koolen, DA, Marcelis, CL, Medeira, A, Micale, L, Mohammed, S, de Munnik, SA, Nordgren, A, Psoni, S, Reardon, W, Revencu, N, Roscioli, T, Ruiterkamp-Versteeg, M, Santos, HG, Schoumans, J, Schuurs-Hoeijmakers, JHM, Silengo, MC, Toledo, L, Vendrell, T, van der Burgt, I, van Lier, B, Zweier, C, Reymond, A, Trembath, RC, Perez-Jurado, L, Dupont, J, de Vries, BBA, Brunner, HG, Veltman, JA, Merla, G, Antonarakis, SE, and Hoischen, A
- Abstract
Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p<0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
- Published
- 2013