The genetic landscape and clinical implication of pediatric Moyamoya angiopathy in an international cohort.

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings.

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.

The magnitude of clinical utility of preconception expanded carrier screening (ECS) concerning its potential to reduce the risk of affected offspring is unknown. Since neurodevelopmental disorders (NDDs) in their offspring is a major concern of parents-to-be, we addressed the question of residual risk by assessing the risk-reduction potential for NDDs in a retrospective study investigating ECS with different criteria for gene selection and definition of pathogenicity. We used exome sequencing data from 700 parents of children with NDDs and blindly screened for carrier-alleles in up to 3046 recessive/X-linked genes.

Active receptor tyrosine kinases, but not Brachyury, are sufficient to trigger chordoma in zebrafish.

The aberrant activation of developmental processes triggers diverse cancer types. Chordoma is a rare, aggressive tumor arising from transformed notochord remnants. Several potentially oncogenic factors have been found to be deregulated in chordoma, yet causation remains uncertain.

Mutations in and genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling.

Bcl9 and Pygopus (Pygo) are obligate Wnt/β-catenin cofactors in , yet their contribution to Wnt signaling during vertebrate development remains unresolved. Combining zebrafish and mouse genetics, we document a conserved, β-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development. Disrupting the β-catenin-BCL9-Pygo complex results in a broadly maintained canonical Wnt response yet perturbs heart development and proper expression of key cardiac regulators.

The Small RNA RyhB Is a Regulator of Cytochrome Expression in .

produces an extensive electron transfer network that results in metabolic flexibility. A large number of -type cytochromes are expressed by and these function as the fundamental electron transport chain proteins. Although several cytochromes have been well-characterized, little is known about how their expression is regulated.