Infantile Convulsions with Paroxysmal Dyskinesia (ICCA Syndrome) and Copy Number Variation at Human Chromosome 16p11

BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome); the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105) located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions

Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species

The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved to an average 16-fold mean coverage by next-generation DNA sequencing technologies. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described thus providing an opportunity for comparison with the completed genomes of pathogenic Leishmania species. A high synteny was observed between all sequenced Leishmania species. A limited number of chromosomal regions diverged between L. tarentolae and L. infantum, while remaining syntenic to L. major. Globally, >90% of the L. tarentolae gene content was shared with the other Leishmania species. We identified 95 predicted coding sequences unique to L. tarentolae and 250 genes that were absent from L. tarentolae. Interestingly, many of the latter genes were expressed in the intracellular amastigote stage of pathogenic species. In addition, genes coding for products involved in antioxidant defence or participating in vesicular-mediated protein transport were underrepresented in L. tarentolae. In contrast to other Leishmania genomes, two gene families were expanded in L. tarentolae, namely the zinc metallo-peptidase surface glycoprotein GP63 and the promastigote surface antigen PSA31C. Overall, L. tarentolae's gene content appears better adapted to the promastigote insect stage rather than the amastigote mammalian stage

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

OBJECTIVE: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. METHODS: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. RESULTS: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. CONCLUSIONS: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutationsjournal articleresearch support, non-u.s. gov't2012 Nov 202012 10 17importedComment in : Paroxysmal disorders associated with PRRT2 mutations shake up expectations on ion channel genes. [Neurology. 2012

Un mélèze fossile dans le sud de la Chartreuse

Abstract. — A flattened larch trunk has been found in sands lying in the middle of the Quaix-Proveysieux cirque, 485 m above sea level, on the Southern side of the Chartreuse massif. From the sedimentological data its deposition can be placed during the recessional fluctuations of the local glacier, after an important erosive phase. Radiocarbon age (> 35.000 years) places these fluctuations during the Wurmian II, before the Wurmian II-III Interstage. The presence of these loose sediments at the center of the small valley rules out a new important glaciation, as they would otherwise have been scraped off; therefore, the Wurmian glacial maximum should antedate the Wurmian III in this part of the Alps.Résumé. — Un tronc de mélèze aplati a été trouvé dans des sables placés au centre du cirque de Quaix-Proveysieux, à 485 m d'altitude, sur le versant méridional de la Chartreuse. La sédimentologie permet de concevoir son dépôt au cours des oscillations de retrait du glacier local, après une phase érosive importante. L'âge, donné par le radiocarbone (> 35 000 ans) autorise à placer ces oscillations au cours du Wurm II, avant l'Interstade Wurm II-III. La présence de ces sédiments meubles au centre du vallon exclut la possibilité du retour d'une importante glaciation qui en aurait effacé les traces; donc le maximum glaciaire wurmien serait antérieur au Wurm III dans cette partie des Alpes.Bocquet A., Colardelle M., Evin Jacques, Rochette P., Uselle J.-P. Un mélèze fossile dans le sud de la Chartreuse. In: Revue de géographie alpine, tome 61, n°4, 1973. pp. 571-582

Incidence and survival of childhood central nervous system tumors: A report of the regional registry of childhood cancers in Auvergne-Limousin

International audienc

Systematic sourcing of granite shafts from Gallia Narbonensis and comparison with other western Mediterranean areas

International audienceDetermining the source quarries for granite shafts in antiquity provides insight into ancient trade routes for such prized materials. We briefly review how non-invasive techniques are currently being applied to address this archeometric task. In specific cases established protocols based on magnetic susceptibility can be integrated with chemical analysis, as demonstrated herein. A systematic inventory and sourcing of granite shafts of presumed antique origin was performed in the region that once formed Gallia Narbonensis. A total of 276 complete shafts or shaft fragments were identified in 21 localities. After fragment pairing hypotheses, they were attributed to at least 174 original shafts. Only four localities (Aix, Arles, Die, Riez) contribute to 54% of the whole corpus. Provenance was determined through visual, magnetic susceptibility and chemical comparison with known antique quarries in Egypt, Turkey, Elba, Corsica and Sardinia. Most of the shafts originated in Turkey (75%), followed by Elba (20.5%). Minor sources are the pink granites of Aswan and Sardinia, as well as grey granite from Corsica, found only in Die. Ambiguity between the Corsican source and the grey Egyptian granite from Mons Claudianus was resolved using portable X-ray fluorescence to determine Sr and Rb contents. As most of the corpus consists of shafts present in medieval to modern contexts, caution is required in interpreting our findings in terms of Ancient Roman architectural and economic choices. Long distance transport of spolia or newly quarried shafts may have occurred after Roman times

Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome

International audienc

Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome

International audienc

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

ObjectiveWhole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine.MethodsWe performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate.ResultsTwo known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura.ConclusionsWe extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations