De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment.

ABSTRACT: CHAMP1 encodes a protein with a function in kinetochore-microtubule attachment and in the regulation of chromosome segregation, both of which are known to be important for neurodevelopment. By trio whole-exome sequencing, we have identified de novo deleterious mutations in CHAMP1 in five unrelated individuals affected by intellectual disability with severe speech impairment, motor developmental delay, muscular hypotonia, and similar dysmorphic features including short philtrum and a tented upper and everted lover lip. In addition to two frameshift and one nonsense mutations, we found an identical nonsense mutation, c.1192C>T (p.Arg398*), in two affected individuals. All mutations, if resulting in a stable protein, are predicted to lead to the loss of the functionally important zinc-finger

SUBMITTER: Hempel M 

PROVIDER: S-EPMC4564986 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature