PubMed 25497044

Referenced in: none

Automatically associated channels: KCNQ2 , Kv7.2

Title: Molecular characterization of a cohort of 73 patients with infantile spasms syndrome.

Authors: Nadia Boutry-Kryza, Audrey Labalme, Dorothee Ville, Julitta de Bellescize, Renaud Touraine, Fabienne Prieur, Sarra Dimassi, Anne-Lise Poulat, Marianne Till, Massimiliano Rossi, Emilie Bourel-Ponchel, Aline Delignières, Anne-Gaelle Le Moing, Clotilde Rivier, Vincent des Portes, Patrick Edery, Alain Calender, Damien Sanlaville, Gaétan Lesca

Journal, date & volume: Eur J Med Genet, 2015 Feb , 58, 51-8

PubMed link:

Infantile Spasms syndrome (ISs) is a characterized by epileptic spasms occurring in clusters with an onset in the first year of life. West syndrome represents a subset of ISs that associates spasms in clusters, a hypsarrhythmia EEG pattern and a developmental arrest or regression. Aetiology of ISs is widely heterogeneous including many genetic causes. Many patients, however, remain without etiological diagnosis, which is critical for prognostic purpose and genetic counselling. In the present study, we performed genetic screening of 73 patients with different types of ISs by array-CGH and molecular analysis of 5 genes: CDKL5, STXBP1, KCNQ2, and GRIN2A, whose mutations cause different types of epileptic encephalopathies, including ISs, as well as MAGI2, which was suggested to be related to a subset of ISs. In total, we found a disease-causing mutation or CNV (Copy Number Variation) in 15% of the patients. These included 6 point mutations found in CDKL5 (n = 3) and STXBP1 (n = 3), 3 microdeletions (10 Mb in 2q24.3, 3.2 Mb in 5q14.3 including the region upstream to MEF2C, and 256 kb in 9q34 disrupting EHMT1), and 2 microduplications (671 kb in 2q24.3 encompassing SCN2A, and 11.93 Mb in Xq28). In addition, we discuss 3 CNVs as potential risk factors, including one 16p12.1 deletion, one intronic deletion of the NEDD4 gene, and one intronic deletion of CALN1 gene. The present findings highlight the efficacy of combined cytogenetic and targeted mutation screening to improve the diagnostic yield in patient with ISs.