Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries.

Purpose: Monogenic rare diseases contribute significantly to infant deaths and pediatric hospitalizations and cause burden to the patients and their families. The American College of Medical Genetics and Genomics recommended in 2021 that carrier screening of autosomal recessive and X-linked conditions with a carrier frequency of ≥1/200 and a severe or moderate phenotype should be offered when planning or during pregnancy. In November 2023 gnomAD v4.

Profiling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels: a cross-sectional study.

Background: Bladder cancer is a highly over-represented disease in males. The involvement of sex steroids in bladder carcinogenesis and the utilisation of steroid hormone action as a therapeutic target have been frequently proposed. However, the intratumoural steroid milieu remains unclear.

Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin.

Objective: Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.

Methods And Analysis: A recurrent OT patient population (n=9) was identified.

A recurrent ACTA1 amino acid change in mosaic form causes milder asymmetric myopathy.

We describe three patients with asymmetric congenital myopathy without definite nemaline bodies and one patient with severe nemaline myopathy. In all four patients, the phenotype had been caused by pathogenic missense variants in ACTA1 leading to the same amino acid change, p.(Gly247Arg).

A novel partial de novo duplication of JARID2 gene causing a neurodevelopmental phenotype.

Background: Deletions covering the entire or partial JARID2 gene as well as pathogenic single nucleotide variants leading to haploinsufficiency of JARID2 have recently been shown to cause a clinically distinct neurodevelopmental syndrome. Here, we present a previously undescribed partial de novo duplication of the JARID2 gene in a patient displaying features similar to those of patients with JARID2 loss-of-function variants.

Case Report: The index patient presents with abnormalities in gross motor skills and speech development as well as neuropsychiatric disorders.

A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign.

Background: PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g.

Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health.

We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects.

Loss-of-function mutation in leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells.

The Ikaros family transcription factors regulate lymphocyte development. Loss-of-function variants in cause primary immunodeficiency, but Ikaros family members and have not yet been associated with immunodeficiency. Here, we describe a pedigree with a heterozygous truncating variant in , encoding the transcriptional activator and repressor Helios, which is highly expressed in regulatory T cells and effector T cells, particularly of the CD8 T cell lineage.

Hereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients.

Background: Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found.

Objectives: To identify mutations underlying PPK in a cohort of 64 patients.

Co-Amorphous Formulations of Furosemide with Arginine and P-Glycoprotein Inhibitor Drugs.

In this study, the amino acid arginine (ARG) and P-glycoprotein (P-gp) inhibitors verapamil hydrochloride (VER), piperine (PIP) and quercetin (QRT) were used as co-formers for co-amorphous mixtures of a Biopharmaceutics classification system (BCS) class IV drug, furosemide (FUR). FUR mixtures with VER, PIP and QRT were prepared by solvent evaporation, and mixtures with ARG were prepared by spray drying in 1:1 and 1:2 molar ratios. The solid-state properties of the mixtures were characterized with X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) in stability studies under different storage conditions.

Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells.

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals' drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage.

A nearly fatal primary Epstein-Barr virus infection associated with low NK-cell counts in a patient receiving azathioprine: a case report and review of literature.

Background: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab.

Case Presentation: An 11-year-old girl presented with chronic, bloody diarrhea.

SNP Analysis of Caries and Initial Caries in Finnish Adolescents.

Background: Dental caries is the most common infection in the world and is influenced by genetic and environmental factors. Environmental factors are largely known, but the role of genetic factors is quite unknown. The aim was to investigate the genetic background of caries in Finnish adolescents.

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland.

: Eosinophilic airway inflammation is common in asthma patients and appears to be associated with severe exacerbations and loss of asthma control. : To describe the resource utilization and clinical characteristics of patients with eosinophilic asthma. : Asthma patients ≥18 years with ≥1 blood eosinophil count in secondary care (South West Finland) during 2003‒2013 were included.

High Beck Depression Inventory 21 scores in adolescents without depression are associated with negative self-image and immature defense style.

Beck Depression Inventory (BDI) is widely used in assessing adolescents' psychological wellbeing, but occasionally the result diverges from diagnostics. Our aim was to identify factors associated with discrepancies between BDI scores and diagnostic assessment in adolescent psychiatric patients and general population. The study comprised 206 inpatients (13-17 years old) and 203 age and gender matched non-referred adolescents.

Who would benefit from exome sequencing?

Next-generation sequencing methods have revolutionized the possibilities for analyzing the human genome. Sequencing the exome, the protein-encoding portion of the genome, is used, in clinical medicine, especially in the diagnosis of rare hereditary diseases, congenital developmental disorders and cancer. Using exome sequencing as a diagnostic test is justified when the results could lead to an accurate diagnosis, significantly influence the treatment and genetic counseling.

Periodontal Initial Radiological Findings of Genetically Predisposed Finnish Adolescents.

Introduction: Periodontitis is a multifactorial infectious disease of the supporting tissues of teeth in which bacterial, genetic and lifestyle factors such as smoking have an important role.

Aim: The aim was to examine if Bleeding On Probing (BOP ≥ 20%) and ≥ 4 mm deep pockets correlated with any suspicion of initial radiological findings of periodontitis and bone loss. We also investigated whether any pro-inflammatory-related candidate Single Nucleotide Polymorphisms (SNPs) were associated with any suspicion of radiological findings.

Towards more consistent and effective food control: learning from the views of food business operators.

We surveyed the opinions of Finnish food business operators (FBOs) about the uniformity of local official food control and its importance for dairy, fishery and meat plants. A total of 136 FBOs responded to the questionnaire. Most FBOs considered official food control to be important for food safety and were generally satisfied with its quality.

Pilot Study on the Genetic Background of an Active Matrix Metalloproteinase-8 Test in Finnish Adolescents.

Background: In periodontitis, genetics and smoking play important roles in host immune system response. The aim of this study is to determine whether the genetic background of initial periodontitis and caries could be detected using an active matrix metalloproteinase (aMMP)-8 chairside test in Finnish adolescents.

Methods: Forty-seven participants gave approval for analysis of both oral fluid collection and DNA.