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

Kinga Hadzsiev, Noemi Polgar, J. Bene, K. Komlósi, Judit Karteszi, Katalin Hollody, G. Kosztolányi, Alessandra Renieri, B. Melegh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)183-187
Number of pages5
JournalJournal of Human Genetics
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Cyclin-Dependent Kinase 5
Rett Syndrome
Phenotype
Mutation
Genes
Terminator Codon
Nonsense Codon
Missense Mutation
Molecular Biology
Epilepsy
Catalytic Domain

Keywords

  • CDKL5
  • FOXG1
  • MECP2
  • Rett syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations. / Hadzsiev, Kinga; Polgar, Noemi; Bene, J.; Komlósi, K.; Karteszi, Judit; Hollody, Katalin; Kosztolányi, G.; Renieri, Alessandra; Melegh, B.

In: Journal of Human Genetics, Vol. 56, No. 3, 03.2011, p. 183-187.

Research output: Contribution to journalArticle

Hadzsiev, Kinga ; Polgar, Noemi ; Bene, J. ; Komlósi, K. ; Karteszi, Judit ; Hollody, Katalin ; Kosztolányi, G. ; Renieri, Alessandra ; Melegh, B. / Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations. In: Journal of Human Genetics. 2011 ; Vol. 56, No. 3. pp. 183-187.
@article{be19e69d18f14c12913b458e10635e61,
title = "Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations",
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.",
keywords = "CDKL5, FOXG1, MECP2, Rett syndrome",
author = "Kinga Hadzsiev and Noemi Polgar and J. Bene and K. Koml{\'o}si and Judit Karteszi and Katalin Hollody and G. Kosztol{\'a}nyi and Alessandra Renieri and B. Melegh",
year = "2011",
month = "3",
doi = "10.1038/jhg.2010.156",
language = "English",
volume = "56",
pages = "183--187",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

AU - Hadzsiev, Kinga

AU - Polgar, Noemi

AU - Bene, J.

AU - Komlósi, K.

AU - Karteszi, Judit

AU - Hollody, Katalin

AU - Kosztolányi, G.

AU - Renieri, Alessandra

AU - Melegh, B.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - CDKL5

KW - FOXG1

KW - MECP2

KW - Rett syndrome

UR - http://www.scopus.com/inward/record.url?scp=79953183967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953183967&partnerID=8YFLogxK

U2 - 10.1038/jhg.2010.156

DO - 10.1038/jhg.2010.156

M3 - Article

C2 - 21160487

AN - SCOPUS:79953183967

VL - 56

SP - 183

EP - 187

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 3

ER -