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Epilepsies have long remained refractory to gene identification due to several obstacles, including a highly variable inter- and intrafamilial expressivity of the phenotypes, a high frequency of phenocopies, and a huge genetic heterogeneity. Recent technological breakthroughs, such as array comparative genomic hybridization and next generation sequencing, have been leading, in the past few years, to the identification of an increasing number of genomic regions and genes in which mutations or copy-number variations cause various epileptic disorders, revealing an enormous diversity of pathophysiological mechanisms. The field that has undergone the most striking revolution is that of epileptic encephalopathies, for which most of causing genes have been discovered since the year 2012. Some examples are the continuous spike-and-waves during slow-wave sleep and Landau-Kleffner syndromes for which the recent discovery of the role of GRIN2Amutations has finally confirmed the genetic bases. These new technologies begin to be used for diagnostic applications, and the main challenge now resides in the interpretation of the huge mass of variants detected by these methods. The identification of causative mutations in epilepsies provides definitive confirmation of the clinical diagnosis, allows accurate genetic counselling, and sometimes permits the development of new appropriate and specific antiepileptic therapies. Future challenges include the identification of the genetic or environmental factors that modify the epileptic phenotypes caused by mutations in a given gene and the understanding of the role of somatic mutations in sporadic epilepsies.

Le Fragile X associated Tremor/Ataxia Syndrome (FXTAS) est lié aux prémutations du gène FMR1 alors que les mutations complètes du même gène sont responsables du syndrome de l’X fragile.

Myotonia is unusual in infants, and not well-known.

To report clinical, neuroradiologic, neurophysiologic, and genetic findings on 16 patients from 11 unrelated families with a remarkable uniform phenotype characterized by infantile ascending hereditary spastic paralysis (IAHSP).

To report a 7-year experience of presymptomatic testing in persons at risk for Huntington disease (HD) and to compare their characteristics and outcomes with those of persons at risk for a less disabling condition, autosomal dominant cerebellar ataxias (ADCA).

BACKGROUND: Hereditary factors have been reported in 5-10% of cases with exocrine pancreatic cancer and recent data support a role for BRCA2. AIMS: We have studied the prevalence of germline BRCA2 mutations in two groups of patients with exocrine pancreatic cancer from an unselected series in Spain: group A included 24 cases showing familial aggregation of cancer and group B included 54 age, sex, and hospital matched cases without such evidence. METHODS: Information was obtained by interview of patients and was validated by a telephone interview with a structured questionnaire. In patients from group A, >80% of the coding sequence of BRCA2 was analysed; in patients from group B, the regions in which germline BRCA2 mutations have been described to be associated with pancreatic cancer were screened. RESULTS: Telephone interviews led to reclassification of 7/54 cases (13%). Familial aggregation of cancer was found in 24/165 cases (14.5%); six patients had a first degree relative with pancreatic cancer (3.6%) and nine patients had relatives with breast cancer. Germline BRCA2 mutations were not identified in any patient from group A (0/23). Among group B cases, one germline variant (T5868G>Asn1880Lys) was found in a 59 year old male without a family history of cancer. The 6174delT mutation was not found in any of the 71 cases analysed. CONCLUSIONS: The overall prevalence of BRCA2 mutations among patients with pancreatic cancer in Spain is low and the 6174delT mutation appears to be very infrequent. Our data do not support screening patients with cancer of the pancreas for germline BRCA2 mutations to identify relatives at high risk of developing this tumour.

Le séquençage du génome est actuellement principalement réalisé à l’aide des nouvelles méthodes de séquençage à haut débit (massive parallel sequencing) qui réduisent considérablement le temps et le coût du séquençage. Néanmoins, la méthode de Sanger reste largement utilisée comme principale méthode de validation de la présence des variants. L’analyse des données issues du séquençage à haut débit nécessite la mise en place et l’utilisation de plusieurs outils bioinformatiques, regroupés en pipelines, académiques ou commerciaux. Nous présentons une méthode statistique permettant de comparer des pipelines et illustrons son utilisation à travers la comparaison d’un pipeline académique (BWA-GATK) et d’un pipeline commercial (TMAP-NextGENe®) en présence ou non d’un gold standard(Sanger). Cette illustration porte sur des données d’un panel de 41 gènes séquencés chez 43 patients atteints d’épilepsie sur un séquenceur Iontorrent (PGM).