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

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 postsy...

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Detalhes bibliográficos
Autores: Nevado, Julián, Pérez Jurado, Luis Alberto, Lapunzina, Pablo Daniel, Spanish PMS Working Group
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/54670
Acesso em linha:http://hdl.handle.net/10230/54670
http://dx.doi.org/10.3389/fgene.2022.652454
Access Level:acceso abierto
Palavra-chave:22q13 deletion syndrome
Phelan-McDermid syndrome (PMS)
SHANK3
Autistic behavior
Intellectual disabilities (ID)
Subtelomeric deletion syndrome
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spelling Variability in Phelan-McDermid syndrome in a cohort of 210 individualsNevado, JuliánPérez Jurado, Luis AlbertoLapunzina, Pablo DanielSpanish PMS Working Group22q13 deletion syndromePhelan-McDermid syndrome (PMS)SHANK3Autistic behaviorIntellectual disabilities (ID)Subtelomeric deletion syndromePhelan-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.Frontiers202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54670http://dx.doi.org/10.3389/fgene.2022.652454reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCopyright © 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/546702026-05-29T05:05:01Z
dc.title.none.fl_str_mv Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
title Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
spellingShingle Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
Nevado, Julián
22q13 deletion syndrome
Phelan-McDermid syndrome (PMS)
SHANK3
Autistic behavior
Intellectual disabilities (ID)
Subtelomeric deletion syndrome
title_short Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
title_full Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
title_fullStr Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
title_full_unstemmed Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
title_sort Variability in Phelan-McDermid syndrome in a cohort of 210 individuals
dc.creator.none.fl_str_mv Nevado, Julián
Pérez Jurado, Luis Alberto
Lapunzina, Pablo Daniel
Spanish PMS Working Group
author Nevado, Julián
author_facet Nevado, Julián
Pérez Jurado, Luis Alberto
Lapunzina, Pablo Daniel
Spanish PMS Working Group
author_role author
author2 Pérez Jurado, Luis Alberto
Lapunzina, Pablo Daniel
Spanish PMS Working Group
author2_role author
author
author
dc.subject.none.fl_str_mv 22q13 deletion syndrome
Phelan-McDermid syndrome (PMS)
SHANK3
Autistic behavior
Intellectual disabilities (ID)
Subtelomeric deletion syndrome
topic 22q13 deletion syndrome
Phelan-McDermid syndrome (PMS)
SHANK3
Autistic behavior
Intellectual disabilities (ID)
Subtelomeric deletion syndrome
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54670
http://dx.doi.org/10.3389/fgene.2022.652454
url http://hdl.handle.net/10230/54670
http://dx.doi.org/10.3389/fgene.2022.652454
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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