Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant.

Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3). Short stature homeobox (SHOX) deficiency is caused by loss or defects of the SHOX gene or its enhancer region.

Preimplantation genetic testing in two Danish couples affected by Peutz-Jeghers syndrome.

Background: Guidelines from the European Hereditary Tumor Group as well as The Danish National Guidelines for Peutz-Jeghers Syndrome (PJS) state that both prenatal diagnosis and preimplantation genetic testing for monogenic disorders (PGT-M) should be offered to patients with PJS. However, only a few cases resulting in viable pregnancies have been published.

Objective: We present two cases of PJS patients going through PGT-M for PJS.

Patients' choices and opinions on chorionic villous sampling and non-invasive alternatives for prenatal testing following preimplantation genetic testing for hereditary disorders: A cross-sectional questionnaire study.

Objective: The aim of this study was to investigate choices of and reasoning behind chorionic villous sampling and opinions on non-invasive prenatal testing among women and men achieving pregnancy following preimplantation genetic testing (PGT) for hereditary disorders.

Methods: A questionnaire was electronically submitted to patients who had achieved a clinical pregnancy following PGT at the Center for Preimplantation Genetic Testing, Aalborg University Hospital, Denmark, between 2017 and 2020.

Results: Chorionic villous sampling was declined by approximately half of the patients.

[Preimplantation genetic testing].

Preimplantation genetic testing (PGT) for known familial monogenetic disease (PGT-M) or structural chromosomal rearrangements (PGT-SR) has evolved into a well-established alternative to prenatal diagnosis. PGT significantly reduces the risk of a pregnancy with an affected foetus. Screening for aneuploidy (PGT-A) used as an add-on to standard IVF treatment of infertile couples is widely used internationally, although its benefit is highly debated.

Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy.

A potential link between GABRD encoding the δ subunit of extrasynaptic GABAA receptors and neurodevelopmental disorders has largely been disregarded due to conflicting conclusions from early studies. However, we identified seven heterozygous missense GABRD variants in 10 patients with neurodevelopmental disorders and generalized epilepsy. One variant occurred in two sibs of healthy parents with presumed somatic mosaicism, another segregated with the disease in three affected family members, and the remaining five occurred de novo in sporadic patients.

Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease.

TARS2 encodes human mitochondrial threonyl tRNA-synthetase that is responsible for generating mitochondrial Thr-tRNAThr and clearing mischarged Ser-tRNAThr during mitochondrial translation. Pathogenic variants in TARS2 have hitherto been reported in a pair of siblings and an unrelated patient with an early onset mitochondrial encephalomyopathy and a combined respiratory chain enzyme deficiency in muscle. We here report five additional unrelated patients with TARS2-related mitochondrial diseases, expanding the clinical phenotype to also include epilepsy, dystonia, hyperhidrosis and severe hearing impairment.

A systematic review on concurrent aneuploidy screening and preimplantation genetic testing for hereditary disorders: What is the prevalence of aneuploidy and is there a clinical effect from aneuploidy screening?

Introduction: In assisted reproductive technology, aneuploidy is considered a primary cause of failed embryo implantation. This has led to the implementation of preimplantation genetic testing for aneuploidy in some clinics. The prevalence of aneuploidy and the use of aneuploidy screening during preimplantation genetic testing for inherited disorders has not previously been reviewed.

[Preimplantation genetic testing for aneuploidy].

This review summarises the current knowledge on preimplantation genetic testing for aneuploidy (PGT-A). Selection and transfer of euploid embryos aim to improve live birth rate (LBR) per embryo transfer, but fluorescence in situ hybridisation-based PGT-A and biopsy of cleavage stage embryos in the 2000s was a disappointment, as studies revealed a reduced LBR. Today, PGT-A includes comprehensive chromosome screening primarily of blastocyst biopsies.

[Preimplantation genetic diagnosis].

In Denmark, preimplantation genetic diagnosis (PGD) is offered within the public healthcare to families with a known risk of an inherited disease in a child - as an alternative to prenatal diagnosis. It is a well-established technique with rather well-described perinatal- and neonatal outcomes, being comparable to what is seen following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The most common strategy is now to perform trophectoderm biopsy and then vitrify, while the diagnostic test is performed.

A method for estimation of plasma albumin concentration from the buffering properties of whole blood.

Purpose: Hypoalbuminemia is strongly associated with poor clinical outcome. Albumin is usually measured at the central laboratory rather than point of care, but in principle, information exists in the buffering properties of whole blood to estimate plasma albumin concentration from point of care measurements of acid-base and oxygenation status. This article presents and evaluates a new method for doing so.