title: Transcription factor 4 and myocyte enhancer factor 2C mutations are not common causes of Rett syndrome.
abstract: The systematic screening of Rett syndrome (RTT) patients for pathogenetic sequence variations has focused on three genes that have been associated with RTT or related clinical phenotypes, namely MECP2, CDKL5, and FOXG1. More recently, it has been suggested that phenotypes associated with TCF4 and MEF2C mutations may represent a form of RTT. Here we report on the screening of the TCF4 and MEF2C genes in a cohort of 81 classical, atypical, and incomplete atypical RTT patients harboring no known mutations in MECP2, CDKL5, and FOXG1 genes. No pathogenetic sequence variations were identified in the MEF2C gene in our cohort. However, a frameshift mutation in TCF4 was identified in a patient with a clinical diagnosis of "variant" RTT, in whom the clinical evolution later raised the possibility of Pitt-Hopkins syndrome. Although our results suggest that these genes are not commonly associated with RTT, we note the clinical similarity between RTT and Pitt-Hopkins syndrome, and suggest that RTT patients with no mutation identified in MECP2 be considered for molecular screening of the TCF4 gene.
authors.affiliation: NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Roksana
authors.initials: R
authors.lastname: Armani
authors.forename: Hayley
authors.initials: H
authors.lastname: Archer
authors.forename: Angus
authors.initials: A
authors.lastname: Clarke
authors.forename: Pradeep
authors.initials: P
authors.lastname: Vasudevan
authors.forename: Christiane
authors.initials: C
authors.lastname: Zweier
authors.forename: Gladys
authors.initials: G
authors.lastname: Ho
authors.forename: Sarah
authors.initials: S
authors.lastname: Williamson
authors.forename: Desiree
authors.initials: D
authors.lastname: Cloosterman
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D019066:Facies; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D006801:Humans; D006985:Hyperventilation / Q000175:diagnosis / Q000235:genetics*; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D026161:MADS Domain Proteins / Q000235:genetics*; D064326:MEF2 Transcription Factors; D008297:Male; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors