Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability

X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. Over the past decade, next-generation sequencing has clearly stimulated the gene discovery process a...

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Autores: Ibarluzea, Nekane|||0000-0003-0951-1686, de la Hoz, Ana Belén, Villate, Olatz, Llano, Isabel|||0000-0001-5576-1227, Ocio, Intzane, Martí, Itxaso|||0000-0003-0578-9568, Guitart, Maria|||0000-0003-2957-7404, Gabau, Elisabeth|||0000-0001-8120-7393, Andrade, Fernando, Gener, Blanca|||0000-0001-8945-812X, Tejada, María Isabel|||0000-0002-7334-1864
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:226167
Acceso en línea:https://ddd.uab.cat/record/226167
https://dx.doi.org/urn:doi:10.3390/genes11010051
Access Level:acceso abierto
Palabra clave:X-linked intellectual disability
Next-generation sequencing
Gene panel
HUWE1
IQSEC2
MED12
PHF8
SLC6A8
SLC9A6
SYN1
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network_name_str España
repository_id_str
spelling Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual DisabilityIbarluzea, Nekane|||0000-0003-0951-1686de la Hoz, Ana BelénVillate, OlatzLlano, Isabel|||0000-0001-5576-1227Ocio, IntzaneMartí, Itxaso|||0000-0003-0578-9568Guitart, Maria|||0000-0003-2957-7404Gabau, Elisabeth|||0000-0001-8120-7393Andrade, FernandoGener, Blanca|||0000-0001-8945-812XTejada, María Isabel|||0000-0002-7334-1864X-linked intellectual disabilityNext-generation sequencingGene panelHUWE1IQSEC2MED12PHF8SLC6A8SLC9A6SYN1X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. Over the past decade, next-generation sequencing has clearly stimulated the gene discovery process and has become part of the diagnostic procedure. We have performed targeted next-generation sequencing of 82 XLID genes on 61 non-related male patients with suggestive non-syndromic XLID. These patients were initially referred to the molecular genetics laboratory to exclude Fragile X Syndrome. The cohort includes 47 male patients with suggestive X-linked family history of ID meaning that they had half-brothers or maternal cousins or uncles affected; and 14 male patients with ID and affected brothers whose mothers show skewed X-inactivation. Sequencing data analysis identified 17 candidate variants in 16 patients. Seven families could be re-contacted and variant segregation analysis of the respective eight candidate variants was performed: HUWE1, IQSEC2, MAOA, MED12, PHF8, SLC6A8, SLC9A6, and SYN1. Our results show the utility of targeted next-generation sequencing in unravelling the genetic origin of XLID, especially in retrospective cases. Variant segregation and additional studies like RNA sequencing and biochemical assays also helped in re-evaluating and further classifying the genetic variants found. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226167https://dx.doi.org/urn:doi:10.3390/genes11010051reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00321open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2261672026-06-06T12:50:31Z
dc.title.none.fl_str_mv Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
title Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
spellingShingle Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
Ibarluzea, Nekane|||0000-0003-0951-1686
X-linked intellectual disability
Next-generation sequencing
Gene panel
HUWE1
IQSEC2
MED12
PHF8
SLC6A8
SLC9A6
SYN1
title_short Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
title_full Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
title_fullStr Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
title_full_unstemmed Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
title_sort Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
dc.creator.none.fl_str_mv Ibarluzea, Nekane|||0000-0003-0951-1686
de la Hoz, Ana Belén
Villate, Olatz
Llano, Isabel|||0000-0001-5576-1227
Ocio, Intzane
Martí, Itxaso|||0000-0003-0578-9568
Guitart, Maria|||0000-0003-2957-7404
Gabau, Elisabeth|||0000-0001-8120-7393
Andrade, Fernando
Gener, Blanca|||0000-0001-8945-812X
Tejada, María Isabel|||0000-0002-7334-1864
author Ibarluzea, Nekane|||0000-0003-0951-1686
author_facet Ibarluzea, Nekane|||0000-0003-0951-1686
de la Hoz, Ana Belén
Villate, Olatz
Llano, Isabel|||0000-0001-5576-1227
Ocio, Intzane
Martí, Itxaso|||0000-0003-0578-9568
Guitart, Maria|||0000-0003-2957-7404
Gabau, Elisabeth|||0000-0001-8120-7393
Andrade, Fernando
Gener, Blanca|||0000-0001-8945-812X
Tejada, María Isabel|||0000-0002-7334-1864
author_role author
author2 de la Hoz, Ana Belén
Villate, Olatz
Llano, Isabel|||0000-0001-5576-1227
Ocio, Intzane
Martí, Itxaso|||0000-0003-0578-9568
Guitart, Maria|||0000-0003-2957-7404
Gabau, Elisabeth|||0000-0001-8120-7393
Andrade, Fernando
Gener, Blanca|||0000-0001-8945-812X
Tejada, María Isabel|||0000-0002-7334-1864
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv X-linked intellectual disability
Next-generation sequencing
Gene panel
HUWE1
IQSEC2
MED12
PHF8
SLC6A8
SLC9A6
SYN1
topic X-linked intellectual disability
Next-generation sequencing
Gene panel
HUWE1
IQSEC2
MED12
PHF8
SLC6A8
SLC9A6
SYN1
description X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. Over the past decade, next-generation sequencing has clearly stimulated the gene discovery process and has become part of the diagnostic procedure. We have performed targeted next-generation sequencing of 82 XLID genes on 61 non-related male patients with suggestive non-syndromic XLID. These patients were initially referred to the molecular genetics laboratory to exclude Fragile X Syndrome. The cohort includes 47 male patients with suggestive X-linked family history of ID meaning that they had half-brothers or maternal cousins or uncles affected; and 14 male patients with ID and affected brothers whose mothers show skewed X-inactivation. Sequencing data analysis identified 17 candidate variants in 16 patients. Seven families could be re-contacted and variant segregation analysis of the respective eight candidate variants was performed: HUWE1, IQSEC2, MAOA, MED12, PHF8, SLC6A8, SLC9A6, and SYN1. Our results show the utility of targeted next-generation sequencing in unravelling the genetic origin of XLID, especially in retrospective cases. Variant segregation and additional studies like RNA sequencing and biochemical assays also helped in re-evaluating and further classifying the genetic variants found.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/226167
https://dx.doi.org/urn:doi:10.3390/genes11010051
url https://ddd.uab.cat/record/226167
https://dx.doi.org/urn:doi:10.3390/genes11010051
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00321
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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