It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge-Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified.
METHODS
We
performed whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge-Weber syndrome. We tested Alpelisib molecular weight for the presence of a somatic mosaic mutation in 97 samples from 50 persons with the Sturge-Weber syndrome, a port-wine stain, or neither (controls), using amplicon sequencing and SNaPshot assays, and investigated the effects of the mutation on downstream signaling, using phosphorylation-specific antibodies for relevant effectors and a luciferase reporter assay.
RESULTS
We identified a nonsynonymous single-nucleotide variant (c.548G -> A, p.Arg183Gln) in GNAQ in samples selleck chemical of affected tissue from 88% of the participants (23 of 26) with the Sturge-Weber syndrome and from 92% of the participants
(12 of 13) with apparently nonsyndromic port-wine stains, but not in any of the samples of affected tissue from 4 participants with an unrelated cerebrovascular malformation or in any of the samples from the 6 controls. The prevalence of the mutant allele in affected tissues ranged from
1.0 to 18.1%. Extracellular signal-regulated kinase activity was modestly increased during transgenic expression of mutant G alpha(q).
CONCLUSIONS
The Sturge-Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. This finding confirms a long-standing hypothesis.”
“Alterations in the ratio between the 2nd and 4th finger digits have been posited as a potential indicator of increased liability for neurodevelopmental disorders such as autism and schizophrenia. SB525334 chemical structure We compared digit ratios in two groups of psychometrically-identified schizotypes, namely, those characterized by positive schizotypy (perceptual aberrations and magical ideation; n = 76) and those characterized by negative schizotypy (social anhedonia; n = 64), to a control group (n = 110). The groups were also compared in terms of their performance on a measure of Theory of Mind, namely, the Reading the Mind in the Eyes Test (RMET) and trait affect, as measured by the PANAS. Our results indicate that neither negative schizotypy nor positive schizotypy is associated with altered digit ratios. Similarly, the groups showed no significant differences on the RMET. However, we observed a small but significant inverse association between Theory of Mind performance and negative affect.