Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes
| Autor: | Saloua Mrabet, Caroline Nava, Imen Kacem, Eric LeGuern, Mouna Ben Djebara, Riadh Gouider, Eric Noé, A. Gargouri-Berrechid, Guillaume Achaz, Zied Landoulsi, Stéphanie Baulac, Fatma Laatar |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Proband Multifactorial Inheritance Candidate gene Tunisia Adolescent Genetic Linkage Pedigree chart Protein Serine-Threonine Kinases Quantitative trait locus Cohort Studies Calcium Channels T-Type Consanguinity Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Childhood absence epilepsy Genetics CACNA1H medicine Humans Family Genetic Predisposition to Disease Age of Onset Child Genetic Association Studies Genetics (clinical) biology Oligogenic Inheritance medicine.disease Pedigree 030104 developmental biology biology.protein Epilepsy Generalized Female Juvenile myoclonic epilepsy Microtubule-Associated Proteins 030217 neurology & neurosurgery |
| Zdroj: | neurogenetics. 19:165-178 |
| ISSN: | 1364-6753 1364-6745 |
| DOI: | 10.1007/s10048-018-0550-z |
| Popis: | Genetic generalized epilepsies (GGE) (childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures (GTCS)) are mainly determined by genetic factors. Since few mutations were identified in rare families with autosomal dominant GGE, a polygenic inheritance was suspected in most patients. Recent studies on large American or European cohorts of sporadic cases showed that susceptibility genes were numerous although their variants were rare, making their identification difficult. Here, we reported clinical and genetic characteristics of 30 Tunisian GGE families, including 71 GGE patients. The phenotype was close to that in sporadic cases. Nineteen pedigrees had a homogeneous type of GGE (JME-CAE-CGTS), and 11 combined these epileptic syndromes. Rare non-synonymous variants were selected in probands using a targeted panel of 30 candidate genes and their segregation was determined in families. Molecular studies incriminated different genes, mainly CACNA1H and MAST4. The segregation of at least two variants in different genes in some pedigrees was compatible with the hypothesis of an oligogenic inheritance, which was in accordance with the relatively low frequency of consanguineous probands. Since at least 2 susceptibility genes were likely shared by different populations, genetic factors involved in the majority of Tunisian GGE families remain to be discovered. Their identification should be easier in families with a homogeneous type of GGE, in which an intra-familial genetic homogeneity could be suspected. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink