MLL2 mutation spectrum in 45 patients with Kabuki syndrome.

TitleMLL2 mutation spectrum in 45 patients with Kabuki syndrome.
Publication TypeJournal Article
Year of Publication2010
AuthorsPaulussen ADC, Stegmann APA, Blok MJ, Tserpelis D, Posma-Velter C, Detisch Y, Smeets EEJGL, Wagemans A, Schrander JJP, van den Boogaard M-JH, van der Smagt J, van Haeringen A, Stolte-Dijkstra I, Kerstjens-Frederikse WS, Mancini GM, Wessels MW, Hennekam RCM, Vreeburg M, Geraedts J, de Ravel T, Fryns J-P, Smeets HJ, Devriendt K, Schrander-Stumpel CTRM
JournalHuman mutation
Date Published2010 Dec 7

Kabuki Syndrome (KS) is a rare syndrome characterized by intellectual disability and multiple congenitali abnormalities, in particular a distinct dysmorphic facial appearance. KS is caused by mutations in the MLL2 genei, encoding an H3K4 histonei methyl transferase which acts as an epigenetici 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.

Alternate JournalHum. Mutat.
Citation Key417