Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy.

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown.

Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE.

Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.

We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.

Weak genetic signal for phenotypic integration implicates developmental processes as major regulators of trait covariation.

Phenotypic integration is an important metric that describes the degree of covariation among traits in a population, and is hypothesized to arise due to selection for shared functional processes. Our ability to identify the genetic and/or developmental underpinnings of integration is marred by temporally overlapping cell-, tissue- and structure-level processes that serve to continually 'overwrite' the structure of covariation among traits through ontogeny. Here, we examine whether traits that are integrated at the phenotypic level also exhibit a shared genetic basis (e.