The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.

Cilia are essential organelles and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis in animals models but remains poorly defined. Notably, all but one subunit of the CPLANE complex have been implicated in human ciliopathy.

Attitudes Towards Non-directiveness Among Medical Geneticists in Germany and Switzerland.

The principle of non-directiveness remains an important tenet in genetics. However, the concept has encountered growing criticism over the last two decades. There is an ongoing discussion about its appropriateness for specific situations in genetics, especially in light of recent significant advancements in genetic medicine.

: A Platform for Clinical-Grade Interpretation of Genetic Variants to Foster Personalized Healthcare in Switzerland.

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows. This includes extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUSs) are a challenge to personalized medicine.

'It's a nightmare': informed consent in paediatric genome-wide sequencing. A qualitative expert interview study from Germany and Switzerland.

The use of genome-wide sequencing (GWS) in paediatrics has added complexity to informed consent (IC) and pretest counselling because of the vast number and interpretation of potential findings, and their implications. However, empirical data from continental Europe on these issues remains limited. This study therefore aimed to explore the experiences and views of medical geneticists working with children in Germany and Switzerland regarding the challenges of obtaining valid IC in paediatric GWS.

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research.

The full spectrum of ethical issues in pediatric genome-wide sequencing: a systematic qualitative review.

Background: The use of genome-wide sequencing in pediatric medicine and research is growing exponentially. While this has many potential benefits, the normative and empirical literature has highlighted various ethical issues. There have not been, however, any systematic reviews of these issues.

Expanding the KIF4A-associated phenotype.

Kinesin super family (KIF) genes encode motor kinesins, a family of evolutionary conserved proteins, involved in intracellular trafficking of various cargoes. These proteins are critical for various physiological processes including neuron function and survival, ciliary function and ciliogenesis, and cell-cycle progression. Recent evidence suggests that alterations in motor kinesin genes can lead to a variety of human diseases, including monogenic disorders.

How genomics is changing the practice of prenatal testing.

New genomic laboratory technology namely microarrays and high throughput sequencing (HTS) as well as a steady progress in sonographic image capture and processing have changed the practice of prenatal diagnosis during the last decade fundamentally. Pregnancies at high risk for common trisomies are reliably identified by non-invasive prenatal testing (NIPT) and expert sonography has greatly improved the assessment of the fetal phenotype. Preconceptional comprehensive carrier screening using HTS is available for all parents, if they should wish to do so.

Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency).

Arts syndrome or phosphoribosyl-pyrophosphate-synthetase-1 (PRPS1) deficiency is caused by loss-of-function mutations in the gene (Xq22.3). PRPS1 is an initial and essential step for the synthesis of the nucleotides of purines, pyrimidines, and nicotinamide.

'Kinesinopathies': emerging role of the kinesin family member genes in birth defects.

Motor kinesins are a family of evolutionary conserved proteins involved in intracellular trafficking of various cargoes, first described in the context of axonal transport. They were discovered to have a key importance in cell-cycle dynamics and progression, including chromosomal condensation and alignment, spindle formation and cytokinesis, as well as ciliogenesis and cilia function. Recent evidence suggests that impairment of kinesins is associated with a variety of human diseases consistent with their functions and evolutionary conservation.

Expanding the spectrum of SMAD3-related phenotypes to agnathia-otocephaly.

Background: Agnathia-otocephaly is a rare and lethal anomaly affecting craniofacial structures derived from the first pharyngeal arch. It is characterized by agnathia, microstomia, aglossia, and abnormally positioned auricles with or without associated anomalies. Variants affecting function of OTX2 and PRRX1, which together regulate the neural crest cells and the patterning of the first pharyngeal arch as well as skeletal and limb development, were identified to be causal for the anomaly in a few patients.

CUGC for Stromme syndrome and CENPF-related disorders.

Stromme syndrome.Jejunal atresia with microcephaly and ocular anomalies.Apple peel syndrome with microcephaly and ocular anomalies.

Fetal arthrogryposis: Challenges and perspectives for prenatal detection and management.

Antenatal identification of fetuses with multiple congenital contractures or arthrogryposis multiplex congenita (AMC) may be challenging. The first clinical sign is often reduced fetal movement and/or contractures, as seen on prenatal ultrasounds. This can be apparent at any point, from early to late pregnancy, may range from mild to severe involvement, with or without associated other structural anomalies.

Exome sequencing of fetal anomaly syndromes: novel phenotype-genotype discoveries.

The monogenic etiology of most severe fetal anomaly syndromes is poorly understood. Our objective was to use exome sequencing (ES) to increase our knowledge on causal variants and novel candidate genes associated with specific fetal phenotypes. We employed ES in a cohort of 19 families with one or more fetuses presenting with a distinctive anomaly pattern and/or phenotype recurrence at increased risk for lethal outcomes.

Loss-of-function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish.

Mutations in KIF14 have previously been associated with either severe, isolated or syndromic microcephaly with renal hypodysplasia (RHD). Syndromic microcephaly-RHD was strongly reminiscent of clinical ciliopathies, relating to defects of the primary cilium, a signalling organelle present on the surface of many quiescent cells. KIF14 encodes a mitotic kinesin, which plays a key role at the midbody during cytokinesis and has not previously been shown to be involved in cilia-related functions.