Novel FOXG1 mutations in Chinese patients with Rett syndrome or Rett-like mental retardation

We aimed to delineate clinical phenotypes associated with FOXG1 mutations in Chinese patients with Rett syndrome (RTT) or RTT-like mental retardation (MR).

Four hundred and fifty-one patients were recruited, including 418 with RTT and 33 with RTT-like MR. Gene mutations were identified by a target capture method and verified by Sanger sequencing.

Four FOXG1 mutations were detected in four patients (three with RTT and one with RTT-like MR), including one previously described mutation and three novel mutations. These mutations included one missense and three micro-insertion mutations. Overall, 0.7% (3/418) of patients who had RTT in our cohort had FOXG1 mutations. All patients had early global developmental delays followed later by severe mental retardation. None of the patients acquired speech or purposeful hand movements, and all of them presented with severe hypotonia, epilepsy, and hypoplasia of the corpus callosum.

Our findings extend the spectrum of FOXG1 mutations and the clinical features of RTT in Chinese patients. We recommend that patients with congenital RTT and Rett-like MR, especially those with brain malformations, such as hypoplasia of the corpus callosum, should be tested for FOXG1 mutations.