Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice

Orphanet Journal of Rare Diseases

Review

Virginia Pérez-Fernández¹  Maria Barreda-Sánchez²  Lluís Armengol-Dulcet³  Lidia Isolina Rodríguez-Peña⁴  María José Sánchez-Soler⁵  Ana Teresa Serrano-Antón⁵  Vanesa López-González⁶  Encarna Guillén-Navarro⁶  María Juliana Ballesta-Martínez⁶ 

[1] Departamento de Ciencias Sociosanitarias-Área de Bioestadística, Facultad de Medicina, Universidad de Murcia, Murcia, Spain;Instituto Murciano de Investigación Biomédica (IMIB), Murcia, Spain;Quantitative Genomic Medicine Laboratories (qGenomics), Esplugues del Llobregat, Catalonia, Spain;Sección de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain;Sección de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain;Instituto Murciano de Investigación Biomédica (IMIB), Murcia, Spain;Sección de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain;Instituto Murciano de Investigación Biomédica (IMIB), Murcia, Spain;Centro de Investigación Biomédica en Red-Enfermedades Raras (CIBERER-Instituto de Salud Carlos III), Madrid, Spain;

关键词: Intellectual disability;    Global developmental delay;    Exome sequencing;    NGS;    Clinical exome sequencing;    Diagnostic yield;    Efficiency;   

DOI  :  10.1186/s13023-023-02809-z

 received in 2023-03-07, accepted in 2023-07-05,  发布年份 2023

来源: Springer

【 摘 要 】

Intellectual disability (ID) has a prevalence of 1–3% and aproximately 30–50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren’t clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.

【 授权许可】

CC BY   
© The Author(s) 2023

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