Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.Neurolog

Seismic studies around the Kola Superdeep Borehole, Russia

The Kola Superdeep Borehole (SG-3) provided an ideal opportunity to test hypotheses on the origins of crustal reflections and on the presence and seismic expression of fluids in the upper crust. The alternative sources of crustal reflections include compositional changes, shear zones, fluids, and metamorphic facies changes, all of which are represented at the well. Both the 38-km-long CDP section and the borehole VSPs in the range 2.2–6.0 km demonstrate the presence of reflections from dipping compositional layering, shear zones, and fluid-filled zones. Subhorizontal reflectivity zones are interpreted as horizontal fluid-filled fracture-type reservoir rocks. Results suggest the presence of fluids down to a depth of at least 12 km in the upper crust; the presence of these fluids lowering seismic velocity causes estimates of upper crustal composition to be too felsic

Project images crust, collects seismic data in world’s largest borehole

An anomaly in our understanding of upper continental crustal structure is caused by conflicting observations from structural geologists and reflection seismologists. Near‐surface structure in metamorphic terrain is frequently steeply dipping or vertical, but seismic reflection images display flat‐lying reflectors below depths of a few kilometers. The seismic image of the topmost 2–3 km is usually blank. How can this be, when seismic reflections are supposed to represent primary geological structure? Seismic measurements in and around a deep borehole could solve this dilemma. Surface seismic observations and physical samples collected from the hole by wireline logging, particularly by vertical seismic profiles (VSPs), could then be compared

Vertical seismic profile results from the Kola Superdeep Borehole, Russia

Multi-offset vertical seismic profiles (VSPs) from the Kola Superdeep Borehole (SG-3), as part of a larger seismic study of the Kola region conducted during the spring of 1992, sample the dipping Pechenga complex from 2175 m to 6000 m and contribute to the understanding of reflectivity in crystalline and Precambrian environments. From the surface to 6000 m, the SG-3 borehole penetrates interlayered Proterozoic metavolcanic and metasedimentary units and a mylonitic shear zone ranging from greenschist to amphibolite metamorphic grade, respectively. The Kola VSPs display a 6% velocity decrease which coincides to a mylonitic shear zone located between 4500 m and 5100 m within the SG-3 borehole. Seismic interfaces are identified by mode-converted energy (PS, and SP transmissions and reflections) in addition to primary seismic phases. The VSP shear wave energy is generated at or near the source by vertical vibrators. P-wave and S-wave reflections are generally detected from the same reflecting horizons, but increases in relative S-wave and SP reflection amplitudes originate at 1900 m, 3800 m, 4500 m, and 5100 m depths. These depths coincide with zones of elevated VpVs and may support the presence of free pore fluid which is reported from initial drilling. For the Proterozoic lithologies sampled by the VSP, reflection events result from five mylonitic shear zones and three lithologic contrasts