Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/112696
Title: Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype
Author: Lucariello, Mario
Vidal, Enrique
Vidal, Silvia
Sáez, Mauricio A.
Roa, Laura
Huertas, Dori
Pineda Marfà, Mercè
Dalfó Capella, Esther
Dopazo, Joaquín
Jurado, Paola
Armstrong i Morón, Judith
Esteller, Manel
Keywords: Síndrome de Rett
Mutació (Biologia)
Fenotip
Seqüència d'aminoàcids
Malalties cerebrals
Rett syndrome
Mutation (Biology)
Phenotype
Amino acid sequence
Brain diseases
Issue Date: Dec-2016
Publisher: Springer Verlag
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1007/s00439-016-1721-3
It is part of: Human Genetics, 2016, vol. 135, num. 12, p. 1343-1354
Related resource: https://doi.org/10.1007/s00439-016-1721-3
URI: http://hdl.handle.net/2445/112696
ISSN: 0340-6717
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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