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, N, de la Hoz, AB, Villate, O, Llano, I, Ocio, I, Marti, I, Guitart, M, Gabau, E, Andrade, F, Gener, B, Tejada, MI
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p2773
Acesso em linha:https://i3pt.portalinvestigacion.com/publicaciones/2773
Access Level:acceso abierto
Palavra-chave:X-linked intellectual disability
next-generation sequencing
gene panel
HUWE1
IQSEC2
MED12
PHF8
SYN1
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spelling Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual DisabilityIbarluzea, Nde la Hoz, ABVillate, OLlano, IOcio, IMarti, IGuitart, MGabau, EAndrade, FGener, BTejada, MIX-linked intellectual disabilitynext-generation sequencinggene panelHUWE1IQSEC2MED12PHF8SYN1X-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.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/2773GenesISSN: 20734425reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p27732026-06-21T15:30:37Z
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, N
X-linked intellectual disability
next-generation sequencing
gene panel
HUWE1
IQSEC2
MED12
PHF8
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, N
de la Hoz, AB
Villate, O
Llano, I
Ocio, I
Marti, I
Guitart, M
Gabau, E
Andrade, F
Gener, B
Tejada, MI
author Ibarluzea, N
author_facet Ibarluzea, N
de la Hoz, AB
Villate, O
Llano, I
Ocio, I
Marti, I
Guitart, M
Gabau, E
Andrade, F
Gener, B
Tejada, MI
author_role author
author2 de la Hoz, AB
Villate, O
Llano, I
Ocio, I
Marti, I
Guitart, M
Gabau, E
Andrade, F
Gener, B
Tejada, MI
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
SYN1
topic X-linked intellectual disability
next-generation sequencing
gene panel
HUWE1
IQSEC2
MED12
PHF8
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 2020
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 https://i3pt.portalinvestigacion.com/publicaciones/2773
url https://i3pt.portalinvestigacion.com/publicaciones/2773
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Genes
ISSN: 20734425
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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