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

Madrigal I, Alvarez-Mora MI, Karlberg O, Rodríguez-Revenga L, Elurbe DM, Rabionet R, Mur A, Pie J, Ballesta F, Sauer S, Syvänen AC, Milà M

J. Clin. Pathol. 67 (12) 1099-1103 [2014-12-00; online 2014-10-02]

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. Whole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes. 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. 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.

NGI Uppsala (SNP&SEQ Technology Platform)

National Genomics Infrastructure

PubMed 25271213

DOI 10.1136/jclinpath-2014-202537

Crossref 10.1136/jclinpath-2014-202537

pii: jclinpath-2014-202537