Transcription Factor 4 and Myocyte Enhancer Factor 2C mutations are not common causes of Rett syndrome

• Published in: American journal of medical genetics. Part A Vol. 158A; no. 4; pp. 713 - 719
• Main Authors: Armani, Roksana, Archer, Hayley, Clarke, Angus, Vasudevan, Pradeep, Zweier, Christiane, Ho, Gladys, Williamson, Sarah, Cloosterman, Desiree, Yang, Nan, Christodoulou, John
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Facies; Female; Frameshift Mutation; Genetic Testing; Humans; Hyperventilation - diagnosis; Hyperventilation - genetics; Intellectual Disability - diagnosis; Intellectual Disability - genetics; MADS Domain Proteins - genetics; Male; MECP2; Medical genetics; Medical sciences; MEF2 Transcription Factors; MEF2C; mutation; Myogenic Regulatory Factors - genetics; Neurology; Pitt-Hopkins syndrome; Rett syndrome; Rett Syndrome - diagnosis; Rett Syndrome - genetics; TCF4; Transcription Factor 4; Transcription Factors - genetics; Nervous system diseases; MEF2C; Pitt—Hopkins syndrome; Genetic disease; Cerebral disorder; Myocyte; MECP2; Central nervous system disease; Rett syndrome; Degenerative disease; TCF4; Mutation; Transcription factor
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.34206

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. © 2012 Wiley Periodicals, Inc.