Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction

A study is conducted to identify two de novo heterozygous missense mutations of a conserved amino acid in the basic region of the TCF4 gene in three subjects with Pitt-Hopkins syndrome (PHS). The findings demonstrate that TCF4 anomalies are responsible for PHS and provide the evidence of a human disorder related to class I basic helix-loop-helix transcription-factor defects.