MECP2 mutations in Czech patients with Rett syndrome and Rett-like phenotypes: novel mutations, genotype-phenotype correlations and validation of high-resolution melting analysis for mutation scanning

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F16%3A10327744" target="_blank" >RIV/00064165:_____/16:10327744 - isvavai.cz</a>

Alternative codes found

RIV/00064190:_____/16:N0000058 RIV/00216208:11110/16:10327744

Result on the web

<a href="http://dx.doi.org/10.1038/jhg.2016.19" target="_blank" >http://dx.doi.org/10.1038/jhg.2016.19</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/jhg.2016.19" target="_blank" >10.1038/jhg.2016.19</a>

Result language

angličtina

Original language name

MECP2 mutations in Czech patients with Rett syndrome and Rett-like phenotypes: novel mutations, genotype-phenotype correlations and validation of high-resolution melting analysis for mutation scanning

Original language description

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by developmental regression with loss of motor, communication and social skills, onset of stereotypic hand movements and often seizures. RTT is primarily caused by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). We established a high-resolution melting (HRM) technique for mutation scanning of the MECP2 gene and performed analyses in Czech patients with RTT, autism spectrum conditions and intellectual disability with Rett-like features. In the cases with confirmed MECP2 mutations, we determined X-chromosome inactivation (XCI), examined the relationships between genotype and clinical severity and evaluated the modifying influence of XCI. Our results demonstrate that HRM analysis is a reliable method for the detection of point mutations, small deletions and duplications in the MECP2 gene. We identified 29 pathogenic mutations in 75 girls, including four novel mutations: c.155_1189del1035; 909_932inv;insC, c.573delC, c.857_858dupAA and c.1163_1200del38. Skewed XCI (ratio >75%) was found in 19.3% of the girls, but no gross divergence in clinical severity was observed. Our findings confirm a high mutation frequency in classic RTT (92%) and a correlation between the MECP2 mutation type and clinical severity. We also demonstrate limitations of XCI in explaining all of the phenotypic differences in RTT.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

—

Project

<a href="/en/project/NT13120" target="_blank" >NT13120: Disorders caused by MECP2 mutations in Czech Republic and other genetic factors influencing their phenotype</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Human Genetics

ISSN

1434-5161

e-ISSN

—

Volume of the periodical

61

Issue of the periodical within the volume

7

Country of publishing house

JP - JAPAN

Number of pages

9

Pages from-to

617-625

UT code for WoS article

000380772800007

EID of the result in the Scopus database

2-s2.0-84979587325