RT Journal Article
SR Electronic
T1 Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 1099
OP 1103
DO 10.1136/jclinpath-2014-202537
VO 67
IS 12
A1 Irene Madrigal
A1 Maria Isabel Alvarez-Mora
A1 Olof Karlberg
A1 Laia Rodríguez-Revenga
A1 Dei M Elurbe
A1 Raquel Rabionet
A1 Antonio Mur
A1 Juan Pie
A1 Francisca Ballesta
A1 Sascha Sauer
A1 Ann-Christine Syvänen
A1 Montserrat Milà
YR 2014
UL http://jcp.bmj.com/content/67/12/1099.abstract
AB 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.