Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype-phenotype correlations in a large cohort of patients.
This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1.
Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations.
KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur.
Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.