Workshop report: Clinical training and integration of genetic counselors into interprofessional teams in the German-speaking countries.

In spring 2022, the inaugural cohort of Genetic and Genomic Counseling MSc students graduated from the Medical University of Innsbruck, representing a significant milestone for the establishment of the genetic counselor (GC) profession in the German-speaking countries. A pivotal component of their education was a 15-week clinical training period. The placement experiences of both students and supervisors offered valuable insights into the attitudes of medical geneticists toward the profession.

Circulating Tumor DNA (ctDNA) Dynamics Predict Early Response to Treatment in Metastasized Gastroesophageal Cancer (mGEC) After 2 Weeks of Systemic Treatment.

Unlabelled: mGEC is associated with poor overall survival (OS) of approximately 4-10 months. CtDNA is emerging as a promising prognostic biomarker with high potential for early relapse detection. However, until now, there was little knowledge on serial ctDNA detection and its impact on early treatment evaluation and prognosis in mGEC.

Non-genetic diagnostic investigations in monogenic Ehlers-Danlos syndromes.

With increased application of Next Generation Sequencing (NGS) in the diagnosis of monogenic Ehlers-Danlos syndromes, there is an increased probability to identify variants of unknown significance. Additionally, in some cases no genetic alteration may be identified whilst there is a strong clinical suspicion on a monogenic EDS type. The diagnostic value of non-genetic investigations, which prior to NGS were quite commonly used to support the clinical diagnosis of monogenic EDS types, is explored.

Clinical diagnosis of the monogenic Ehlers-Danlos syndromes.

Monogenic Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue conditions that are clinically characterised by joint hypermobility, skin hyperextensibility and/or fragility, and generalised tissue fragility. Gene panel testing with massively parallel sequencing is currently gold standard to confirm diagnoses of the monogenic EDS types. We aim to report on the (combination of) clinical features of the monogenic EDS types through text and photographs, to aid clinical diagnosis as despite the significant progress in genetic testing possibilities, a thorough clinical assessment which includes medical history, family history and physical examination remains important in the diagnostic process.

First experiences with the introduction of genetic counselors in human genetic services in the German-speaking countries.

In 2019, the Medical University of Innsbruck introduced the first Genetic and Genomic Counseling master's program in the German-speaking countries. A major challenge of this process was the absence of practicing Genetic Counselors (GC) in these countries, leading to a lack of experience with GCs in medical genetic services and the absence of a legal framework for the profession. Consequently, student placements within the program commenced with neither the students nor their supervising consultants having any previous experience of collaborative teamwork between clinical geneticists and GCs.

Steatotic liver disease associated with 2,4-dienoyl-CoA reductase 1 deficiency.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered multifactorial with a number of predisposing gene polymorphisms known.

Methods: The occurrence of MASLD in 7 and 10 year old siblings, one without classical risk factors and one with type 2 diabetes suggested a monogenic etiology and prompted next-generation sequencing. Exome sequencing was performed in the proband, both parents and both siblings.

Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcomes.

Background: Homologous recombination deficiency (HRD) has evolved into a major diagnostic marker in high-grade ovarian cancer (HGOC), predicting the response to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences the treatment response and patient survival; miliary type tumor spread has a poorer predicted outcome than non-miliary type tumor spread.

Methods: Known methods for HRD assessment were adapted for our technical requirements and the predictive-value integrated genomic instability score (PIGIS) for HRD assessment evolved as an outcome.

Sleep-stage dependence and co-existence of cardio-respiratory coordination and phase synchronization.

Interactions between the cardiac and respiratory systems play a pivotal role in physiological functioning. Nonetheless, the intricacies of cardio-respiratory couplings, such as cardio-respiratory phase synchronization (CRPS) and cardio-respiratory coordination (CRC), remain elusive, and an automated algorithm for CRC detection is lacking. This paper introduces an automated CRC detection algorithm, which allowed us to conduct a comprehensive comparison of CRPS and CRC during sleep for the first time using an extensive database.

Knock-out of dipeptidase CN2 in human proximal tubular cells disrupts dipeptide and amino acid homeostasis and para- and transcellular solute transport.

Aim: Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase-2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. We therefore hypothesized, that CN2 has a key metabolic role, impacting proximal tubular transport function.

Filaggrin gene variants among Saudi patients with ichthyosis vulgaris.

Ichthyoses are a heterogeneous group of cornification disorders. The most common form of ichthyoses is ichthyosis vulgaris (IV) ([OMIM] #146,700), which can be inherited as autosomal semi-dominant mutation in the filaggrin gene (FLG). We present the findings of a study involving 35 Saudi patients with a clinical diagnosis of ichthyosis vulgaris.

[Diagnosis and treatment of focal-segmental glomerulosclerosis-2023].

The histopathological term focal-segmental glomerulosclerosis comprises different pathogenic processes with the unifying features of a high proteinuria and the name-giving glomerular lesion pattern seen on light microscopy. A differentiation according to the underlying cause into primary, secondary and genetic forms is therefore of utmost importance. The pathogenesis of primary focal-segmental glomerulosclerosis remains unknown but, like minimal-change disease, an autoimmune-mediated process leading to podocyte damage is assumed.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants.

Automatic sleep-stage classification of heart rate and actigraphy data using deep and transfer learning approaches.

Manual sleep-stage scoring based on full-night polysomnography data recorded in a sleep lab has been the gold standard of clinical sleep medicine. This costly and time-consuming approach is unfit for long-term studies as well as assessment of sleep on a population level. With the vast amount of physiological data becoming available from wrist-worn devices, deep learning techniques provide an opportunity for fast and reliable automatic sleep-stage classification tasks.

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/050, May 2022).

The aim of this guideline is to standardize the diagnosis and therapy of recurrent miscarriage (RM) using evidence from the recent literature. This is done by using consistent definitions, objective evaluations and standardized treatment protocols. When this guideline was compiled, special consideration was given to previous recommendations in prior versions of this guideline and the recommendations of the European Society of Human Reproduction and Embryology, the Royal College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine, and a detailed individual search of the literature about the different topics was carried out.

Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.

Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in and , which encode components of the complement system. Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia.

Degradation of collagen I by activated C1s in periodontal Ehlers-Danlos Syndrome.

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, lack of attached gingiva and thin and fragile gums leading to gingival recession. Connective tissue abnormalities of pEDS typically include easy bruising, pretibial plaques, distal joint hypermobility, hoarse voice, and less commonly manifestations such as organ or vessel rupture. pEDS is caused by heterozygous missense mutations in and genes of the classical complement C1 complex.