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Title: MLL2 mutation spectrum in 45 patients with Kabuki syndrome
Authors: Paulussen, Aimée D C ×
Stegmann, Alexander P A
Blok, Marinus J
Tserpelis, Demis
Posma-Velter, Crool
Detisch, Yvonne
Smeets, Eric E J G L
Wagemans, Annemieke
Schrander, Jaap J P
van den Boogaard, Marie-José H
van der Smagt, Jasper
van Haeringen, Arie
Stolte-Dijkstra, Irene
Kerstjens-Frederikse, Wilhelmina S
Mancini, Grazia M
Wessels, Marja W
Hennekam, Raoul C M
Vreeburg, Maaike
Geraedts, Joep
de Ravel de l'Argentière, Thomy
Fryns, Jean-Pierre
Smeets, Hubert J
Devriendt, Koenraad
Schrander-Stumpel, Constance T R M #
Issue Date: Feb-2011
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation vol:32 issue:2 pages:E2018-E2025
Article number: 10.1002/humu.21416
Abstract: Kabuki Syndrome (KS) is a rare syndrome characterized by intellectual disability and multiple congenital abnormalities, in particular a distinct dysmorphic facial appearance. KS is caused by mutations in the MLL2 gene, encoding an H3K4 histone methyl transferase which acts as an epigenetic transcriptional activator during growth and development. Direct sequencing of all 54 exons of the MLL2 gene in 45 clinically well-defined KS patients identified 34 (75.6%) different mutations. One mutation has been described previously, all others are novel. Clinically, all KS patients were sporadic, and mutations were de novo for all 27 families for which both parents were available. We detected nonsense (n=11), frameshift (n=17), splice site (n=4) and missense (n=2) mutations, predicting a high frequency of absent or non-functional MLL2 protein. Interestingly, both missense mutations located in the C-terminal conserved functional domains of the protein. Phenotypically our study indicated a statistically significant difference in the presence of a distinct facial appearance (p=0.0143) and growth retardation (p=0.0040) when comparing KS patients with an MLL2 mutation compared to patients without a mutation. Our data double the number of MLL2 mutations in KS reported so far and widen the spectrum of MLL2 mutations and disease mechanisms in KS. © 2010 Wiley-Liss, Inc.
URI: 
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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