A national long-read sequencing study on chromosomal rearrangements uncovers hidden complexities.

Clinical genetic laboratories often require a comprehensive analysis of chromosomal rearrangements/structural variants (SVs), from large events like translocations and inversions to supernumerary ring/marker chromosomes and small deletions or duplications. Understanding the complexity of these events and their clinical consequences requires pinpointing breakpoint junctions and resolving the derivative chromosome structure. This task often surpasses the capabilities of short-read sequencing technologies.

Modelling the Effects of Forest use Change on Brownification of Finnish Rivers under Atmospheric Pressure.

Browning of surface waters due to increased terrestrial loading of dissolved organic matter (DOM) is observed across the Northern Hemisphere. The effects influence several ecosystem services from freshwater productivity to water purification. Brownification is often explained by changes in large-scale anthropogenic pressures and ecosystem functioning (acidification, climate change, and land cover changes).

Acute disseminated encephalomyelitis following the COVID-19 vaccine Ad26.COV2.S, a case report.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has been leading to dramatic health, social and economic problems around the world. It was necessary to introduce worldwide vaccination program against SARS-CoV-2 virus. Vaccination of billions of people around the world leads to many questions about risk of vaccines and possible side effects.

Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort.

Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease-causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions.

Identification of known and novel familial cancer genes in Swedish colorectal cancer families.

Identifying new candidate colorectal cancer (CRC) genes and mutations are important for clinical cancer prevention as well as in cancer care. Genetic counseling is already implemented for known high-risk variants; however, the majority of CRC are of unknown causes. In our study, 110 CRC patients in 55 Swedish families with a strong history of CRC but unknown genetic causes were analyzed with the aim of identifying novel candidate CRC predisposing genes.

Update on genetic predisposition to colorectal cancer and polyposis.

The present article summarizes recent developments in the characterization of genetic predisposition to colorectal cancer (CRC). The main themes covered include new hereditary CRC and polyposis syndromes, non-CRC hereditary cancer genes found mutated in CRC patients, strategies used to identify novel causal genes, and review of candidate genes that have been proposed to predispose to CRC and/or colonic polyposis. We provide an overview of newly described genes and syndromes associated with predisposition to CRC and polyposis, including: polymerase proofreading-associated polyposis, NTHL1-associated polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations as a rare cause of hereditary nonpolyposis CRC.

Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition.

Purpose: Some 10% of familial adenomatous polyposis (FAP) and 80% of attenuated polyposis (AFAP) cases remain molecularly unexplained. We scrutinized such cases by exome-wide and targeted methods to search for novel susceptibility genes.

Methods: Exome sequencing was conducted on 40 unexplained (mainly sporadic) cases with FAP or AFAP from Finland.

Acute Intravenous Calcium Antagonist for Suspected Hemiplegic Migraine - A Case Story.

Stroke mimics, like attacks of hemiplegic migraine, are challenging in acute stroke evaluation. We present a 28-year-old woman with a suspected hemiplegic migraine attack with left-sided hemiparalysis. Brain CT with perfusion imaging 1 h 54 min after symptom onset revealed hypoperfusion in the right hemisphere.

Systemic Thrombolysis in Acute Ischemic Stroke after Dabigatran Etexilate Reversal with Idarucizumab-A Case Report.

Introduction: Idarucizumab is a reversal agent for dabigatran etexilate. By reversing the anticoagulating effect of dabigatran etexilate with idarucizumab (Praxbind), patients presenting with an acute ischemic stroke can now be eligible for thrombolysis.

Patient: We describe our experience with idarucizumab in a 71-year-old male patient pretreated with dabigatran etexilate.

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e.

Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups.

GREM1 and POLE variants in hereditary colorectal cancer syndromes.

Hereditary factors are thought to play a role in at least one third of patients with colorectal cancer (CRC) but only a limited proportion of these have mutations in known high-penetrant genes. In a relatively large part of patients with a few or multiple colorectal polyps the underlying genetic cause of the disease is still unknown. Using exome sequencing in combination with linkage analyses together with detection of copy-number variations (CNV), we have identified a duplication in the regulatory region of the GREM1 gene in a family with an attenuated/atypical polyposis syndrome.

[Cerebral infarct eight months after primary Varicella-zoster virus infection].

Ischemic stroke is a recognised complication of Varicella-zoster virus (VZV) infections. We report on an otherwise healthy four-year-old boy who presented with acute neurological symptoms due to cerebral infarction eight months after primary VZV infection. Magnetic resonance imaging showed an infarct located to the left nucleus lentiformis.

Eight-and-a-half syndrome as presenting sign of childhood multiple sclerosis.

We present a case of a 12-year-old boy with eight-and-a-half syndrome that consequently proved to be a sign of childhood multiple sclerosis.

A mutation in POLE predisposing to a multi-tumour phenotype.

Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase ε have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed.

Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease.

Purpose: To investigate genotype-phenotype correlation and to analyze functional and structural changes in the retina of patients with von Hippel-Lindau (VHL) disease.

Methods: Thirteen patients from four families (A, B, C and D) with known VHL disease and known mutations in the VHL gene were examined. All patients underwent clinical examination and optical coherence tomography (OCT).

Integrative genetic characterization and phenotype correlations in pheochromocytoma and paraganglioma tumours.

Background: About 60% of Pheochromocytoma (PCC) and Paraganglioma (PGL) patients have either germline or somatic mutations in one of the 12 proposed disease causing genes; SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127, MAX and H-RAS. Selective screening for germline mutations is routinely performed in clinical management of these diseases. Testing for somatic alterations is not performed on a regular basis because of limitations in interpreting the results.