Sequencing of the exome ― coding regions of the human genome ― is used to identify the genetic basis of Kabuki syndrome in a paper published this week in Nature Genetics. This is among the first few examples of using exome sequencing to identify the genes underlying a rare disorder.
Kabuki syndrome is a rare malformation disorder, with an estimated frequency of 1 in 32,000 births in Japan. Kabuki is characterized by distinctive facial features and mild mental retardation.
Jay Shendure and colleagues report high coverage exome sequencing of 10 individuals with Kabuki syndrome. They used a filtering approach to screen the genetic variants identified through sequencing for those likely to be associated with this disorder, and confirmed by targeted sequencing in additional cases. They identified variants in the gene MLL2 as a major cause of Kabuki syndrome.