Marwa Ben Jdila1, Abir Ben Issa2, Boudour Khabou3, Bochra Ben Rhouma4, Fatma Kamoun5, Leila Ammar-Keskes4, Chahnez Triki5, Faiza Fakhfakh6. 1. Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Tunisia; Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia; Unité de recherche de Neuro-Pédiatrie (UR12ES 16) C.H.U. He'di Chaker de Sfax, Tunisia. Electronic address: benjdilamarwa@yahoo.com. 2. Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Tunisia; Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia; Unité de recherche de Neuro-Pédiatrie (UR12ES 16) C.H.U. He'di Chaker de Sfax, Tunisia. 3. Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Tunisia; Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia. 4. Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia. 5. Service de Neurologie Infantile, C.H.U. He'di Chaker de Sfax, Tunisia; Unité de recherche de Neuro-Pédiatrie (UR12ES 16) C.H.U. He'di Chaker de Sfax, Tunisia. 6. Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Tunisia. Electronic address: faiza.fakhfakh02@gmail.com.
Abstract
INTRODUCTION: West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. METHODS: The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. RESULTS: The results revealed a complex genotype with more than one mutation in each patient including the known mutations c.1910C>G (P2, P3); c.2372A>C in P3 and c.2395C>G in P1 and novel variants including c.616G>A, shared by the three patients P1, P2 and P3; c.1403G>C shared by P2 and P3 and c.2288A>G in patient P1. CONCLUSIONS: All the mutations were at somatic mosaic state and were de novo in the patients except ones (c.2372A>C). To our knowledge; the somatic mosaic state is described for the first time in patients with West syndrome. Five identified mutations were located in the C-terminal domain of the protein, while the novel mutation (c.616G>A) was in the catalytic domain. Bioinformatic tools predicted that this latter is the most pathogenic substitution affecting 3D protein structure and the secondary mRNA structure. Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability.
INTRODUCTION:West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. METHODS: The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. RESULTS: The results revealed a complex genotype with more than one mutation in each patient including the known mutations c.1910C>G (P2, P3); c.2372A>C in P3 and c.2395C>G in P1 and novel variants including c.616G>A, shared by the three patients P1, P2 and P3; c.1403G>C shared by P2 and P3 and c.2288A>G in patient P1. CONCLUSIONS: All the mutations were at somatic mosaic state and were de novo in the patients except ones (c.2372A>C). To our knowledge; the somatic mosaic state is described for the first time in patients with West syndrome. Five identified mutations were located in the C-terminal domain of the protein, while the novel mutation (c.616G>A) was in the catalytic domain. Bioinformatic tools predicted that this latter is the most pathogenic substitution affecting 3D protein structure and the secondary mRNA structure. Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability.
Authors: Luciana Musante; Paola Costa; Caterina Zanus; Flavio Faletra; Flora M Murru; Anna M Bianco; Martina La Bianca; Giulia Ragusa; Emmanouil Athanasakis; Adamo P d'Adamo; Marco Carrozzi; Paolo Gasparini Journal: Genes (Basel) Date: 2022-03-12 Impact factor: 4.096