Transcript capture and ultradeep long-read RNA sequencing (CAPLRseq) to diagnose HNPCC/Lynch syndrome.

Purpose: Whereas most human genes encode multiple mRNA isoforms with distinct function, clinical workflows for assessing this heterogeneity are not readily available. This is a substantial shortcoming, considering that up to 25% of disease-causing gene variants are suspected of disrupting mRNA splicing or mRNA abundance. Long-read sequencing can readily portray mRNA isoform diversity, but its sensitivity is relatively low due to insufficient transcriptome penetration.

Filler Models Revisited: Extension of the Nielson Model with Respect to the Geometric Arrangements of Fillers.

Models describing how fillers affect the barrier properties of polymers remain an important research topic to improve applications such as hydrogen storage or food preservation. The Nielsen model, one of the earliest models for such predictions, is still one of the most widely used in the literature. However, it does not provide quantitative information on arrangements of fillers inside a polymer matrix, which is crucial for the definition of suitable filler distributions in barrier materials.

Splicing analyses for variants in MMR genes: best practice recommendations from the European Mismatch Repair Working Group.

Over 20% of the DNA mismatch repair (MMR) germline variants in suspected Lynch syndrome patients are classified as variants of uncertain significance (VUS). Well-established functional assays are pivotal for assessing the biological impact of these variants and provide relevant evidence for clinical classification. In our collaborative European Mismatch Repair Working Group (EMMR-WG) we compared three different experimental approaches for evaluating the effect of seven variants on mRNA splicing in MMR genes: (i) RT-PCR of full-length transcripts (FLT), (ii) RT-PCR of targeted transcript sections (TTS), both from patient biological samples and (iii) minigene splicing assays.

Long-term chemoprevention in patients with adenomatous polyposis coli: an observational study.

Prospective short-term studies on effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) point towards a decrease in the number and size of polyps. Effectiveness and safety in the prevention of progression in familial polyposis with NSAIDs in long-term use, which is the prerequisite for therapeutic evaluation in prospective studies, is unknown. The total absolute observation period of 54 patients under sulindac was 399 patient years with a mean of 7.

Constitutional chromothripsis of the locus as a cause of genetic predisposition to colon cancer.

Purpose: Approximately 20% of patients with clinical familial adenomatous polyposis (FAP) remain unsolved after molecular genetic analysis of the and other polyposis genes, suggesting additional pathomechanisms.

Methods: We applied multidimensional genomic analysis employing chromosomal microarray profiling, optical mapping, long-read genome and RNA sequencing combined with FISH and standard PCR of genomic and complementary DNA to decode a patient with an attenuated FAP that had remained unsolved by Sanger sequencing and multigene panel next-generation sequencing for years.

Results: We identified a complex 3.