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

Genes

AnaBelén de la Hoz¹  Fernando Andrade¹  Olatz Villate¹  María-Isabel Tejada¹  Blanca Gener¹  Nekane Ibarluzea¹  Isabel Llano¹  Intzane Ocio²  Itxaso Martí³  Miriam Guitart⁴  Elisabeth Gabau⁴ 

[1] Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain;Department of Paediatric Neurology, Araba University Hospital, Osakidetza Basque Health Service, 01009 Gasteiz, Spain;Department of Paediatric Neurology, Donostia University Hospital, Osakidetza Basque Health Service, 20014 Donostia, Spain;Genetics Laboratory, Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain;

关键词: x-linked intellectual disability;    next-generation sequencing;    gene panel;    huwe1;    iqsec2;    med12;    phf8;    slc6a8;    slc9a6;    syn1;   

DOI  :  10.3390/genes11010051

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown