Irene Madrigal1, Maria Isabel Alvarez-Mora1, Olof Karlberg2, Laia Rodríguez-Revenga1, Dei M Elurbe1, Raquel Rabionet3, Antonio Mur4, Juan Pie5, Francisca Ballesta6, Sascha Sauer7, Ann-Christine Syvänen2, Montserrat Milà1. 1. Biochemistry and Molecular Genetics Department, Hospital Clínic and IDIBAPS, Barcelona, Spain Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain. 2. Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 3. Centre for Genomic Regulation (CRG) and UPF and CIBERESP, Barcelona, Spain. 4. Paediatrics Service, Hospital Universitario del Mar, Barcelona, Spain Paediatrics and Obstetrics Department, Universidad de Barcelona, Barcelona, Spain. 5. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology, Medical School, University of Zaragoza, Zaragoza, Spain. 6. Biochemistry and Molecular Genetics Department, Hospital Clínic and IDIBAPS, Barcelona, Spain. 7. Max-Planck Institute for Molecular Genetics, Berlin, Germany.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Silvia Baldacci; Michele Santoro; Anna Pierini; Lorena Mezzasalma; Francesca Gorini; Alessio Coi Journal: Int J Environ Res Public Health Date: 2022-06-21 Impact factor: 4.614