Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/45131

TitleIdentification of novel genetic causes of Rett syndrome-like phenotypes
Author(s)Lopes, Fátima Daniela Teixeira
Barbosa, Mafalda Fernanda Cabral Santos
Soares, Gabriela
Sá, Joaquim de
Dias, Ana Isabel
Oliveira, Guiomar
Cabral, Pedro
Temudo, Teresa
Maciel, P.
KeywordsRett syndrome
Epilepsy
Whole exome sequencing
Intellectual disability
Issue date9-Feb-2016
PublisherBMJ Publishing Group
JournalJournal of Medical Genetics
CitationLopes, F., Barbosa, M., Ameur, A., Soares, G., De Sá, J., Dias, A. I., . . . Maciel, P. (2016). Identification of novel genetic causes of Rett syndrome-like phenotypes. Journal of Medical Genetics, 53(3), 190-199. doi: 10.1136/jmedgenet-2015-103568
Abstract(s)Background The aim of this work was to identify new genetic causes of Rett-like phenotypes using array comparative genomic hybridisation and a whole exome sequencing approach. Methods and results We studied a cohort of 19 Portuguese patients (16 girls, 3 boys) with a clinical presentation significantly overlapping Rett syndrome (RTT). Genetic analysis included filtering of the single nucleotide variants and indels with preference for de novo, homozygous/compound heterozygous, or maternally inherited X linked variants. Examination by MRI and muscle biopsies was also performed. Pathogenic genomic imbalances were found in two patients (10.5%): an 18q21.2 deletion encompassing four exons of the TCF4 gene and a mosaic UPD of chromosome 3. Variants in genes previously implicated in neurodevelopmental disorders (NDD) were identified in six patients (32%): de novo variants in EEF1A2, STXBP1 and ZNF238 were found in three patients, maternally inherited X linked variants in SLC35A2, ZFX and SHROOM4 were detected in two male patients and one homozygous variant in EIF2B2 was detected in one patient. Variants were also detected in five novel NDD candidate genes (26%): we identified de novo variants in the RHOBTB2, SMARCA1 and GABBR2 genes; a homozygous variant in EIF4G1; compound heterozygous variant in HTT. Conclusions Network analysis reveals that these genes interact by means of protein interactions with each other and with the known RTT genes. These findings expand the phenotypical spectrum of previously known NDD genes to encompass RTT-like clinical presentations and identify new candidate genes for RTT-like phenotypes.
TypeArticle
URIhttp://hdl.handle.net/1822/45131
DOI10.1136/jmedgenet-2015-103568
ISSN0022-2593
Publisher versionhttp://bmj.com/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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