We postulate that Kabuki syndrome may produce this type of ocular phenotype as a result of extensive interaction between KMT2D, WAR complex proteins and PAXIP1.
Kabuki syndrome (KS) is a multiple congenital anomalies syndrome characterized by characteristic facial features and varying degrees of mental retardation, caused by mutations in KMT2D/MLL2 and KDM6A/UTX genes.
To elucidate further the molecular characteristics of Korean patients with KS, we screened a cohort of patients with clinically defined KS for mutations in KMT2D and KDM6A.
The facial features of patients in the MLL2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical.
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.
Our results indicate that MLL2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations and strongly suggest further genetic heterogeneity.
These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki syndrome.