Variability in Phelan-McDermid syndrome in a cohort of 210 individuals

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• dc.contributor.author Nevado, Julián
• dc.contributor.author Pérez Jurado, Luis Alberto
• dc.contributor.author Lapunzina, Pablo Daniel
• dc.contributor.author Spanish PMS Working Group
• dc.date.accessioned 2022-11-03T07:23:46Z
• dc.date.available 2022-11-03T07:23:46Z
• dc.date.issued 2022
• dc.description.abstract Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and SHANK3 sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (de novo or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with SHANK3 variants. Our findings suggest that SHANK3 plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.
• dc.format.mimetype application/pdf
• dc.identifier.citation Nevado J, García-Miñaúr S, Palomares-Bralo M, Vallespín E, Guillén-Navarro E, Rosell J, et al. Variability in Phelan-McDermid syndrome in a cohort of 210 individuals. Front Genet. 2022 Apr 12; 13: 652454. DOI: 10.3389/fgene.2022.652454.
• dc.identifier.doi http://dx.doi.org/10.3389/fgene.2022.652454
• dc.identifier.issn 1664-8021
• dc.identifier.uri http://hdl.handle.net/10230/54670
• dc.language.iso eng
• dc.publisher Frontiers
• dc.rights Copyright © 2022 Nevado, García-Miñaúr, Palomares-Bralo, Vallespín, Guillén-Navarro, Rosell, Bel-Fenellós, Mori, Milá, Campo, Barrúz, Santos-Simarro, Obregón, Orellana, Pachajoa, Tenorio, Galán, Cigudosa, Moresco, Saleme, Castillo, Gabau, Pérez-Jurado, Barcia, Martín, Mansilla, Vallcorba, García-Murillo, Cammarata-Scalisi, Gonçalves Pereira, Blanco-Lago, Serrano, Ortigoza-Escobar, Gener, Seidel, Tirado, Lapunzina and Spanish PMS Working Group. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword 22q13 deletion syndrome
• dc.subject.keyword Phelan-McDermid syndrome (PMS)
• dc.subject.keyword SHANK3
• dc.subject.keyword Autistic behavior
• dc.subject.keyword Intellectual disabilities (ID)
• dc.subject.keyword Subtelomeric deletion syndrome
• dc.title Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion