Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes. Issue 12 (30th September 2014)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of clinical pathology. Volume 67:Issue 12(2014)
• Page Start: 1099
• Page End: 1103
• Publication Date: 2014-09-30
• Subjects: MOLECULAR GENETICS -- GENETICS -- DIAGNOSTICS; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jclinpath-2014-202537
• Languages: English
• ISSNs: 0021-9746

Abstract

Abstract : 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.