@article {558,
	title = {Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype.},
	journal = {Hum Genet},
	volume = {135},
	year = {2016},
	month = {2016 12},
	pages = {1343-1354},
	abstract = {<p>Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6~\%) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes.</p>},
	keywords = {Adolescent, Adult, Animals, Caenorhabditis elegans, Carrier Proteins, Cell Cycle Proteins, Child, Child, Preschool, DNA Mutational Analysis, Exome, Female, Forkhead Transcription Factors, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Methyl-CpG-Binding Protein 2, mutation, Nerve Tissue Proteins, Protein Serine-Threonine Kinases, Receptors, Nicotinic, Rett Syndrome},
	issn = {1432-1203},
	doi = {10.1007/s00439-016-1721-3},
	author = {Lucariello, Mario and Vidal, Enrique and Vidal, Silvia and Saez, Mauricio and Roa, Laura and Huertas, Dori and Pineda, Merc{\`e} and Dalf{\'o}, Esther and Dopazo, Joaquin and Jurado, Paola and Armstrong, Judith and Esteller, Manel}
}
@article {524,
	title = {Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient.},
	journal = {Epigenetics},
	volume = {7},
	year = {2012},
	month = {2012 Jun 01},
	pages = {542-50},
	abstract = {<p>The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable to analyze single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base pair resolution. Genome-wide we detected a decrease of methylation level of 42\%, with the most profound changes occurring in inactive heterochromatic regions, satellite repeats and transposons. Interestingly, transcriptional active loci and ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss of DNA methylation the epigenetic landscape and crucial regulatory structures were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we could associate alterations in promoter methylation with the ICF syndrome immunodeficient phenotype by detecting changes in genes related to the B-cell receptor mediated maturation pathway.</p>},
	keywords = {B-Lymphocytes, Cell Line, Transformed, Child, Preschool, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, Epigenesis, Genetic, Face, Female, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Immunologic Deficiency Syndromes, mutation, Primary Immunodeficiency Diseases, Sequence Analysis, DNA, Sulfites},
	issn = {1559-2308},
	doi = {10.4161/epi.20523},
	author = {Heyn, Holger and Vidal, Enrique and Sayols, Sergi and Sanchez-Mut, Jose V and Moran, Sebastian and Medina, Ignacio and Sandoval, Juan and Sim{\'o}-Riudalbas, Laia and Szczesna, Karolina and Huertas, Dori and Gatto, Sole and Matarazzo, Maria R and Dopazo, Joaquin and Esteller, Manel}
}
