Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
Ibarluzea, Nekane (Centro de Investigación Biomédica en Red de Enfermedades Raras)
de la Hoz, Ana Belén (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Villate, Olatz (Hospital Universitario de Cruces (Barakaldo, País Basc))
Llano, Isabel (Hospital Universitario de Cruces (Barakaldo, País Basc))
Ocio, Intzane (Arabako Unibertsitate Ospitalea (Vitoria, País Basc))
Martí, Itxaso (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Guitart, Míriam (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Gabau, Elisabeth (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Andrade, Fernando (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Gener, Blanca (Hospital Universitario de Cruces (Barakaldo, País Basc))
Tejada, María-Isabel (Hospital Universitario de Cruces (Barakaldo, País Basc))

Date:	2020
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI14/00321
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	X-linked intellectual disability ; Next-generation sequencing ; Gene panel ; HUWE1 ; IQSEC2 ; MED12 ; PHF8 ; SLC6A8 ; SLC9A6 ; SYN1
Published in:	Genes, Vol. 11 (january 2020) , ISSN 2073-4425

DOI: 10.3390/genes11010051
PMID: 31906484

22 p, 2.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles