Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes

• Published in: Journal of clinical pathology Vol. 67; no. 12; pp. 1099 - 1103
• Main Authors: Madrigal, Irene, Alvarez-Mora, Maria Isabel, Karlberg, Olof, Rodríguez-Revenga, Laia, Elurbe, Dei M, Rabionet, Raquel, Mur, Antonio, Pie, Juan, Ballesta, Francisca, Sauer, Sascha, Syvänen, Ann-Christine, Milà, Montserrat
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.12.2014
• Subjects: Adult; Costs; Disease; DNA Mutational Analysis - methods; Exome; Female; Gene Expression Profiling - methods; Genes; Genomes; Humans; Intellectual disabilities; Intellectual Disability - genetics; Male; Mutation; Pedigree; Studies; Syndrome; Transcriptome; GENETICS; MOLECULAR GENETICS; DIAGNOSTICS
• ISSN: 0021-9746; 1472-4146; 1472-4146
• DOI: 10.1136/jclinpath-2014-202537

Aims The causes of intellectual disability, which affects 1%–3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases. Methods Whole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes. Results We present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose. Conclusions The accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.