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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.

Similares en LA Referencia