MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study

P. Makrythanasis; B. W. van Bon; M. Steehouwer; B. Rodríguez-Santiago; M. Simpson; P. Dias; B. M. Anderlid; P. Arts; M. Bhat; B. Augello; E. Biamino; E. M H F Bongers; M. del Campo; I. Cordeiro; A. M. Cueto-González; I. Cuscó; C. Deshpande; E. Frysira; L. Izatt; R. Flores; E. Galán; B. Gener; C. Gilissen; S. M. Granneman; J. Hoyer; H. G. Yntema; C. M. Kets; D. A. Koolen; C. L. Marcelis; A. Medeira; L. Micale; S. Mohammed; S. A. de Munnik; A. Nordgren; S. Psoni; W. Reardon; N. Revencu; T. Roscioli; M. Ruiterkamp-Versteeg; H. G. Santos; J. Schoumans; J. H M Schuurs-Hoeijmakers; M. C. Silengo; L. Toledo; T. Vendrell; I. van der Burgt; B. van Lier; C. Zweier; A. Reymond; R. C. Trembath; L. Perez-Jurado; J. Dupont; B. B A de Vries; H. G. Brunner; J. A. Veltman; G. Merla; S. E. Antonarakis; A. Hoischen

doi:10.1111/cge.12081

MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study

P. Makrythanasis, B. W. van Bon, M. Steehouwer, B. Rodríguez-Santiago, M. Simpson, P. Dias, B. M. Anderlid, P. Arts, M. Bhat, B. Augello, E. Biamino, E. M H F Bongers, M. del Campo, I. Cordeiro, A. M. Cueto-González, I. Cuscó, C. Deshpande, E. Frysira, L. Izatt, R. FloresE. Galán, B. Gener, C. Gilissen, S. M. Granneman, J. Hoyer, H. G. Yntema, C. M. Kets, D. A. Koolen, C. L. Marcelis, A. Medeira, L. Micale, S. Mohammed, S. A. de Munnik, A. Nordgren, S. Psoni, W. Reardon, N. Revencu, T. Roscioli, M. Ruiterkamp-Versteeg, H. G. Santos, J. Schoumans, J. H M Schuurs-Hoeijmakers, M. C. Silengo, L. Toledo, T. Vendrell, I. van der Burgt, B. van Lier, C. Zweier, A. Reymond, R. C. Trembath, L. Perez-Jurado, J. Dupont, B. B A de Vries, H. G. Brunner, J. A. Veltman, G. Merla, S. E. Antonarakis, A. Hoischen

IRCCS Casa Sollievo della Sofferenza

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	539-545
Number of pages	7
Journal	Clinical Genetics
Volume	84
Issue number	6
DOIs	https://doi.org/10.1111/cge.12081
Publication status	Published - Dec 2013

Keywords

Genotype-phenotype correlation
Kabuki syndrome
MLL2
Niikawa-Kuroki syndrome

ASJC Scopus subject areas

Genetics(clinical)
Genetics

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10.1111/cge.12081

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Makrythanasis, P., van Bon, B. W., Steehouwer, M., Rodríguez-Santiago, B., Simpson, M., Dias, P., Anderlid, B. M., Arts, P., Bhat, M., Augello, B., Biamino, E., Bongers, E. M. H. F., del Campo, M., Cordeiro, I., Cueto-González, A. M., Cuscó, I., Deshpande, C., Frysira, E., Izatt, L., ... Hoischen, A. (2013). MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study. Clinical Genetics, 84(6), 539-545. https://doi.org/10.1111/cge.12081

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 2013, 'MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study', Clinical Genetics, vol. 84, no. 6, pp. 539-545. https://doi.org/10.1111/cge.12081

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title = "MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study",

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",

keywords = "Genotype-phenotype correlation, Kabuki syndrome, MLL2, Niikawa-Kuroki syndrome",

author = "P. Makrythanasis and {van Bon}, {B. W.} and M. Steehouwer and B. Rodr{\'i}guez-Santiago and M. Simpson and P. Dias and Anderlid, {B. M.} and P. Arts and M. Bhat and B. Augello and E. Biamino and Bongers, {E. M H F} and {del Campo}, M. and I. Cordeiro and Cueto-Gonz{\'a}lez, {A. M.} and I. Cusc{\'o} and C. Deshpande and E. Frysira and L. Izatt and R. Flores and E. Gal{\'a}n and B. Gener and C. Gilissen and Granneman, {S. M.} and J. Hoyer and Yntema, {H. G.} and Kets, {C. M.} and Koolen, {D. A.} and Marcelis, {C. L.} and A. Medeira and L. Micale and S. Mohammed and {de Munnik}, {S. A.} and A. Nordgren and S. Psoni and W. Reardon and N. Revencu and T. Roscioli and M. Ruiterkamp-Versteeg and Santos, {H. G.} and J. Schoumans and Schuurs-Hoeijmakers, {J. H M} and Silengo, {M. C.} and L. Toledo and T. Vendrell and {van der Burgt}, I. and {van Lier}, B. and C. Zweier and A. Reymond and Trembath, {R. C.} and L. Perez-Jurado and J. Dupont and {de Vries}, {B. B A} and Brunner, {H. G.} and Veltman, {J. A.} and G. Merla and Antonarakis, {S. E.} and A. Hoischen",

year = "2013",

month = dec,

doi = "10.1111/cge.12081",

language = "English",

volume = "84",

pages = "539--545",

journal = "Clinical Genetics",

issn = "0009-9163",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

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TY - JOUR

T1 - MLL2 mutation detection in 86 patients with Kabuki syndrome

T2 - A genotype-phenotype study

AU - Makrythanasis, P.

AU - van Bon, B. W.

AU - Steehouwer, M.

AU - Rodríguez-Santiago, B.

AU - Simpson, M.

AU - Dias, P.

AU - Anderlid, B. M.

AU - Arts, P.

AU - Bhat, M.

AU - Augello, B.

AU - Biamino, E.

AU - Bongers, E. M H F

AU - del Campo, M.

AU - Cordeiro, I.

AU - Cueto-González, A. M.

AU - Cuscó, I.

AU - Deshpande, C.

AU - Frysira, E.

AU - Izatt, L.

AU - Flores, R.

AU - Galán, E.

AU - Gener, B.

AU - Gilissen, C.

AU - Granneman, S. M.

AU - Hoyer, J.

AU - Yntema, H. G.

AU - Kets, C. M.

AU - Koolen, D. A.

AU - Marcelis, C. L.

AU - Medeira, A.

AU - Micale, L.

AU - Mohammed, S.

AU - de Munnik, S. A.

AU - Nordgren, A.

AU - Psoni, S.

AU - Reardon, W.

AU - Revencu, N.

AU - Roscioli, T.

AU - Ruiterkamp-Versteeg, M.

AU - Santos, H. G.

AU - Schoumans, J.

AU - Schuurs-Hoeijmakers, J. H M

AU - Silengo, M. C.

AU - Toledo, L.

AU - Vendrell, T.

AU - van der Burgt, I.

AU - van Lier, B.

AU - Zweier, C.

AU - Reymond, A.

AU - Trembath, R. C.

AU - Perez-Jurado, L.

AU - Dupont, J.

AU - de Vries, B. B A

AU - Brunner, H. G.

AU - Veltman, J. A.

AU - Merla, G.

AU - Antonarakis, S. E.

AU - Hoischen, A.

PY - 2013/12

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N2 - 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

AB - 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

KW - Genotype-phenotype correlation

KW - Kabuki syndrome

KW - MLL2

KW - Niikawa-Kuroki syndrome

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JO - Clinical Genetics

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ER -

MLL2 mutation detection in 86 patients with Kabuki syndrome: A genotype-phenotype study

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Keywords

ASJC Scopus subject areas

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