Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

15Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6). Of the 22 mutations, we identified 7 (31.8) frameshift-causing deletions, 4 (18.2) nonsense, 10 (45.5) missense mutations and one insertion (4.5). The most frequent pathologic changes were: p.Thr158Met (14.2) and p.Arg133Cys (11.9) missense, and p.Arg255Stop (9.5) and p.Arg294Stop (9.5) nonsense mutations. We also detected the c.925C>T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G>T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G>T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations. © 2011 The Japan Society of Human Genetics. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

Hadzsiev, K., Polgar, N., Bene, J., Komlosi, K., Karteszi, J., Hollody, K., … Melegh, B. (2011). Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations. Journal of Human Genetics, 56(3), 183–187. https://doi.org/10.1038/jhg.2010.156

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free