Expanding the genetic landscape of Usher syndrome type IV caused by pathogenic ARSG variants.

Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes.

Establishing Expectancy Values for Fibrin Monomer in Uncomplicated Pregnancy.

 During pregnancy, a physiological increase of molecular activation markers (MAM) of hemostasis such as prothrombin fragments 1 + 2, thrombin-antithrombin complex, and D-dimers (DD) occurs. Therefore, monitoring MAM levels during pregnancy to evaluate the risk of venous thromboembolism (VTE) may be unreliable; nevertheless, DD analysis in pregnancy is widely performed. In contrast to DD, fibrin monomer (FM) levels have been reported to remain stable during pregnancy.

Defining a metrologically traceable and sustainable calibration hierarchy of international normalized ratio for monitoring of vitamin K antagonist treatment in accordance with International Organization for Standardization (ISO) 17511:2020 standard: communication from the International Federation of Clinical Chemistry and Laboratory Medicine-SSC/ISTH working group on prothrombin time/international normalized ratio standardization.

Calibration of prothrombin time (PT) in terms of international normalized ratio (INR) has been outlined in "Guidelines for thromboplastins and plasmas used to control oral anticoagulant therapy" (World Health Organization, 2013). The international standard ISO 17511:2020 presents requirements for manufacturers of in vitro diagnostic (IVD) medical devices (MDs) for documenting the calibration hierarchy for a measured quantity in human samples using a specified IVD MD. The objective of this article is to define an unequivocal, metrologically traceable calibration hierarchy for the INR measured in plasma as well as in whole blood samples.

Identification of Seven Additional Genome Segments of Grapevine-Associated Jivivirus 1.

Jiviruses are a group of recently described viruses characterized with a tripartite genome and having affinities with (RNA1 and 2) and (RNA3). Using a combination of high-throughput sequencing, datamining and RT-PCR approaches, we demonstrate here that in grapevine samples infected by grapevine-associated jivivirus 1 (GaJV-1) up to 7 additional molecules can be consistently detected with conserved 5' and 3' non-coding regions in common with the three previously identified GaJV-1 genomic RNAs. RNA4, RNA5, RNA6, RNA7, RNA8 and RNA10, together with a recombinant RNArec7-8, are all members of a family sharing a previously non recognized conserved protein domain, while RNA9 is part of a distinct family characterized by another conserved motif.

Clinical use of thrombin generation assays.

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations.

Thrombin generation assays are versatile tools in blood coagulation analysis: A review of technical features, and applications from research to laboratory routine.

Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g.

Measuring residual anti-Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa.

Introduction: Andexanet alfa (AnXa) was developed for anticoagulant effect reversal of direct factor Xa inhibitors (DXaI) (apixaban, rivaroxaban, edoxaban) in emergency situations. Regular anti-Xa assays are not suitable to evaluate anti-Xa activity after AnXa administration because of the high sample dilution resulting in the AnXa-DXaI dissociation which gives inaccurately high DXaI measured concentrations. This study aimed at developing dedicated STA-Liquid anti-Xa test set-ups for accurately measuring DXaI after reversal with AnXa.

Effects of circadian variation, lifestyle and environment on hematological parameters: A narrative review.

The complete blood count (CBC) is the most widely prescribed laboratory test. It plays a key role in screening, diagnosing, and monitoring a variety of medical disorders. Preanalytical and analytical variables are responsible for more than 50% of laboratory errors that may lead to spurious CBC results.

Evaluation of DOAC Filter, a new device to remove direct oral anticoagulants from plasma samples.

Introduction: Directs oral anticoagulants (DOACs) can interfere with coagulation assays, especially in thrombophilia workup. To avoid these interferences, a new device, DOAC Filter, allows the removal of DOACs from citrated plasma. This study aims to confirm that DOAC Filter efficiently removes DOACs and to ascertain that coagulation assays are not impacted by filtration.

How I investigate basophilia in daily practice.

Basophilia is a rare disorder of the complete blood count (CBC) and its management in daily practice remains unclear. Two main factors explain this situation. On the one hand, the reliability of the basophil count is insufficient, whether it is performed by a microscopic slide examination or by a hematology analyser.

Clot waveform analysis: Where do we stand in 2017?

Analysis of the optical waveform generated during global coagulation assays, such as activated partial thromboplastin time and prothrombin time, can provide much precious information on the global coagulation state of the plasma sample tested, in addition to a single clotting time. Many studies have been published concerning patient diagnosis and management in haemophilia A, and in the early diagnosis and prognosis of disseminated intravascular coagulation and sepsis. However, many other works have also been published on further potential clinical applications such as lupus anticoagulant diagnosis and anticoagulant monitoring.

Determination of edoxaban equivalent concentrations in human plasma by an automated anti-factor Xa chromogenic assay.

Introduction: This phase I, open-label, multiple-dose, two-treatment study assessed the relationship between edoxaban equivalent concentration derived from an anti-FXa assay with the summed concentration of edoxaban and its active metabolite, M-4, as assessed by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This study also assessed the relationship between edoxaban plasma concentrations assessed by LC/MS/MS in sodium citrate and lithium heparin tubes.

Materials And Methods: Healthy volunteers were randomized to receive once-daily edoxaban 60mg or 90mg for 5days (15 participants per treatment group).

Mutations in Splicing Factor Genes Are a Major Cause of Autosomal Dominant Retinitis Pigmentosa in Belgian Families.

Purpose: Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition.

Methods: Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization).

Factor VII Deficiency: From Basics to Clinical Laboratory Diagnosis and Patient Management.

Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels.

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma.

Background: Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP).

An augmented ABCA4 screen targeting noncoding regions reveals a deep intronic founder variant in Belgian Stargardt patients.

Autosomal-recessive Stargardt disease (STGD1) is hallmarked by a large proportion of patients with a single heterozygous causative variant in the disease gene ABCA4. Braun et al. () reported deep intronic variants of ABCA4 in STGD1 patients with one coding variant, prompting us to perform an augmented screen in 131 Belgian STGD1 patients with one or no ABCA4 variant to uncover deep intronic causal ABCA4 variants.

Identity-by-descent-guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy.

Purpose: Autosomal recessive retinal dystrophies are clinically and genetically heterogeneous, which hampers molecular diagnosis. We evaluated identity-by-descent-guided Sanger sequencing or whole-exome sequencing in 26 families with nonsyndromic (19) or syndromic (7) autosomal recessive retinal dystrophies to identify disease-causing mutations.

Methods: Patients underwent genome-wide identity-by-descent mapping followed by Sanger sequencing (16) or whole-exome sequencing (10).

Congenital fixed dilated pupils due to ACTA2- multisystemic smooth muscle dysfunction syndrome.

Congenital fixed dilated pupils (congenital mydriasis) is characterized by hypoplasia or aplasia of the iris muscles, with absence of iris between the collarette and pupillary border, creating a scalloped pupillary margin. This condition has been reported in a multisystemic smooth muscle cell dysfunction syndrome, combined with congenital patent ductus arteriosus, cerebrovascular disease (Moya-moya-like), coronary artery disease, thoracic aorta aneurysm, and dysfunction of smooth muscle cells in organs throughout the body. All affected individuals carry a p.

Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes.

Purpose: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported.

[Two new anticoagulants available in 2010--Dabigatran Etexilate and Rivaroxaban: expected progresses--raised problems].

After having been used for decades, heparins (unfractionated heparin [UFH] or low molecular weight heparins [LMWH]) and vitamin K antagonists (VKA), which are only parenterally active or which are responsible for frequent iatrogenicity respectively, have to face the competition of new anticoagulant drugs targeting either factor Xa or factor IIa (thrombin). Rivaroxaban (Xarelto(®)) and Dabigatran Etexilate (Pradaxa(®)) are the two leading components. They are more convenient to use and do not require routine coagulation monitoring.

Comparison of a direct Factor Xa inhibitor, edoxaban, with dalteparin and ximelagatran: a randomised controlled trial in healthy elderly adults.

Introduction: Edoxaban (the free base of DU-176b) is a new, oral direct Factor Xa inhibitor. This is the first study to compare the hemostatic response to edoxaban, ximelagatran, and dalteparin in healthy, elderly adults.

Materials And Methods: In this open-label, active-controlled clinical trial, 40 adults (65-75 years), were randomised to: oral edoxaban (60 mg, twice-daily, 7 doses), subcutaneous dalteparin (5000 IU, once-daily, 4 doses), oral ximelagatran (24 mg, twice-daily, 7 doses) or no drug.

LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma.

The latent TGFbeta-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGFbeta-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome.