It is presently known that KMT2D (also known as MLL2) genei mutation is responsible for approximately 75% of individuals with Kabuki Syndrome. More recently, mutations of the KDM6A gene have been discovered in 9% of individuals who tested negative for KMT2D gene mutation. Interestingly, the functions of KDM6A and KMT2D are related to each other. They function by either adding (in the case of KMT2D ) an activating methylgroup or removing (in the case of KDM6A) repressive methyl groupsi to specific amino acids in a protein called Histonei H3. The H3 protein can either be modified by repressive (H3K27me3) or active (H3K4me3) methyl groups. Since the KMT2D and KDM6A genesi have mutations, the KMT2D is not adding the active methyl-groups or KDM6A is not removing the repressive groups. In essence, although they are doing the opposite activity, the result is the same – repressing the open chromatini state of the H3 protein. As a result, the cells in the body that require gene activation through H3 protein, must now do without.
To help families
better understand the basics of the discovery please see Understanding the
Genetics of Kabuki and Epigenetics and How it Relates to Kabuki Syndrome. It is speculated that Kabuki is a heterogeneous
syndrome, meaning that multiple genes could potentially be involved. It is
hoped that with continued analysis, other genes will be discovered.