Screening for MECP2 mutations in females with autistic disorder

Autistic Disorder (AD) and Rett Disorder (RD) are both Pervasive Developmental Disorders. Recently, it was discovered that mutations in the MECP2 gene cause RD. Because of the phenotypic similarity between RD and AD, we screened 69 females in families ascertained for AD. A clinical diagnosis of AD in each patient was confirmed using the ADI-R. Patients with RD features, such as microcephaly, had been excluded from this dataset. Patients were screened for MECP2 variants using DHPLC followed by sequencing. Mutations in the MECP2 gene were identified in two females. Patient one (age 10 years) developed normally until age 30 months when she regressed in language and motor skills. Head circumference is at the 25th percentile. She did not lose purposeful hand movements and never developed RD stereotyped hand movements. She has a 1047C > T nonsense mutation resulting in an R293X aa change and premature protein truncation. Patient two (age 16 years) developed normally until 18 months when problems in response to social and language stimuli were noted. Head circumference is at the 50th percentile. She never developed RD stereotyped hand movements. She is heterozygous for a 41 bp deletion at 1324-1364del, resulting in a frameshift and protein truncation. Mutations in both patients are de novo. These results suggest all females presenting with AD should be screened for MECP2 mutations.

Duke Scholars

Author Allison Elizabeth Ashley-Koch Medicine, Nephrology