A mutation screen in patients with Kabuki syndrome

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• Kabuki syndrome (KS) is a recognized multiple anomaly/mental retardation syndrome.
• KS is characterized by distinctive facial features, developmental delay, short stature, and urogenital anomalies.

Purpose of the Study:

• To investigate the role of the MLL2 gene in Kabuki syndrome.
• To identify mutations in the MLL2 gene in patients with KS.

Main Methods:

• Sequencing of all 54 coding exons of the MLL2 gene in 34 KS patients.
• Analysis of mutation types and locations within the MLL2 gene.
• Comparison of clinical symptoms between MLL2 mutation carriers and non-carriers.

Main Results:

• Identified 18 distinct MLL2 mutations in 19 out of 34 patients; 11 were de novo.
• Mutations included nonsense, splice-site, deletion/insertion, and missense types.
• MLL2 carriers showed a higher incidence of short stature and renal anomalies, and a trend towards typical facial features.

Conclusions:

• MLL2 is the major causative gene for Kabuki syndrome.
• A wide spectrum of de novo MLL2 mutations underlies KS.
• Further genetic heterogeneity may exist in mutation-negative KS cases.