RT Journal Article SR Electronic T1 Identification of novel genetic causes of Rett syndrome-like phenotypes JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 190 OP 199 DO 10.1136/jmedgenet-2015-103568 VO 53 IS 3 A1 Fátima Lopes A1 Mafalda Barbosa A1 Adam Ameur A1 Gabriela Soares A1 Joaquim de Sá A1 Ana Isabel Dias A1 Guiomar Oliveira A1 Pedro Cabral A1 Teresa Temudo A1 Eulália Calado A1 Isabel Fineza Cruz A1 José Pedro Vieira A1 Renata Oliveira A1 Sofia Esteves A1 Sascha Sauer A1 Inger Jonasson A1 Ann-Christine Syvänen A1 Ulf Gyllensten A1 Dalila Pinto A1 Patrícia Maciel YR 2016 UL http://jmg.bmj.com/content/53/3/190.abstract AB 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.