How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum.
Eur J Hum Genet. 2011 Nov 30;
Authors: Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N, Parker MJ, Crow YJ, Kerr B, Kingston H, Metcalfe K, Chandler K, Magee A, Stewart F, McConnell VP, Donnelly DE, Berland S, Houge G, Morton JE, Oley C, Revencu N, Park SM, Davies SJ, Fry AE, Lynch SA, Gill H, Schweiger S, Lam WW, Tolmie J, Mohammed SN, Hobson E, Smith A, Blyth M, Bennett C, Vasudevan PC, García-Miñaúr S, Henderson A, Goodship J, Wright MJ, Fisher R, Gibbons R, Price SM, C de Silva D, Temple IK, Collins AL, Lachlan K, Elmslie F, McEntagart M, Castle B, Clayton-Smith J, Black GC, Donnai D
In this study, researchers looked at the extent of the genetic heterogeneity by comparing KS patients with and without a mutation in KMT2D (formerly known as MLL2), thereby analyzing the potential genotype-phenotype correlations.
The majority of KMT2D mutations were truncating mutations. Nontruncating mutations seen in KS consisted of missense or in-frame insertions or deletions in KMT2D. Splice-site mutations have appeared in a small number of patients.
Genotype-phenotype differences between MLL2 mutation-positive and -negative cases were most significant in clinical features, such as kidney abnormalities, cleft palate, joint dislocations, feeding problems, as well as, early breast buds/gynaecomastia. Less significant were cardiac defects and repeated infections.