Modeling the polar motion of Titan

The angular momentum of the atmosphere and of the hydrocarbon lakes of Titan have a large equatorial component that can excite polar motion, a variable orientation of the rotation axis of Titan with respect to its surface. We here use the angular momentum obtained from a General Circulation Model of the atmosphere of Titan and from an Ocean Circulation Model for Titan's polar lakes to model the polar motion of Titan as a function of the interior structure. Besides the gravitational torque exerted by Saturn on Titan's aspherical mass distribution, the rotational model also includes torques arising due to the presence of an ocean under a thin ice shell as well as the influence of the elasticity of the different layers. The Chandler wobble period of a solid and rigid Titan without its atmosphere is about 279 years. The period of the Chandler wobble is mainly influenced by the atmosphere of Titan (-166 years) and the presence of an internal global ocean (+135 to 295 years depending on the internal model) and to a lesser extent by the elastic deformations (+3.7 years). The forced polar motion of a solid and rigid Titan is elliptical with an amplitude of about 50 m and a main period equal to the orbital period of Saturn. It is mainly forced by the atmosphere of Titan while the lakes of Titan are at the origin of a displacement of the mean polar motion, or polar offset. The subsurface ocean can largely increase the polar motion amplitude due to resonant amplification with a wobble free mode of Titan. The amplitudes as well as the main periods of the polar motion depend on whether and which forcing period is close to the period of a free mode. For a thick ice shell, the polar motion mainly has an annual period and an amplitude of about 1 km. For thinner ice shells, the polar motion amplitude can reach several tens of km and shorter periods become dominant. We demonstrate that for thick ice shells, the ice shell rigidity weakly influences the amplitude of the polar motion. For thin ice shells, the level of the resonant amplification of the polar motion amplitude depends on the ice shell rigidity. Future observations of the polar motion of Titan could help constraining some properties of its interior structure as the ice shell thickness and ocean density

C5orf42 is the major gene responsible for OFD syndrome type VI

Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies

The landscape of epilepsy-related GATOR1 variants

Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway Methods: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants. Results: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign. Conclusion: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP