Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort study.

Background: One in four pregnancies end in a pregnancy loss. Although the effect on couples is well documented, evidence-based treatments and prediction models are absent. Fetal aneuploidy is associated with a higher chance of a next successful pregnancy compared with euploid pregnancy loss in which underlying maternal conditions might be causal.

National data on the early clinical use of non-invasive prenatal testing in public and private healthcare in Denmark 2013-2017.

Introduction: In Denmark, non-invasive prenatal testing (NIPT) has been used since 2013. We aimed to evaluate the early clinical use of NIPT in Danish public and private healthcare settings before NIPT became an integrated part of the national guidelines on prenatal screening and diagnosis in 2017.

Material And Methods: NIPT data were collected between March 2013 and June 2017 from national public registries and private providers.

Characteristics of patients with familial Mediterranean fever in Denmark: a retrospective nationwide register-based cohort study.

To investigate epidemiology, demography, and genetic and clinical characteristics of patients with familial Mediterranean fever (FMF) in Denmark. In this population-based, cross-sectional cohort study, we identified FMF patients from discharge diagnoses using ICD-10 codes in the Danish National Patient Register, and linked data from the Danish Civil Registration System and laboratory databases for results of gene variant screening. We identified 495 FMF patients (prevalence 1:11 680) with a median age of 29 years and a female ratio of 51%.

Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies.

Study Question: Is the fetal fraction (FF) of circulating cell-free DNA (cfDNA) affected in pregnancies following ART treatment with either fresh or frozen embryo transfer (ET) compared with natural conception?

Summary Answer: This study shows a significant reduction in the FF in ART patients compared with naturally conceived pregnancies, which seems to be more pronounced after fresh ET compared with frozen ET.

What Is Known Already: Non-invasive prenatal testing (NIPT) is based on cfDNA in maternal blood, of which about 10% is of placental origin and thus represents the fetal karyotype. Validation studies have demonstrated a high sensitivity, specificity and positive predictive value of NIPT for the detection of fetal trisomy 21, 18 and 13.

Noninvasive prenatal testing and maternal obesity: A review.

Noninvasive prenatal testing (NIPT) has become a popular screening test for the most common fetal aneuploidies. The performance of NIPT is affected by several factors including maternal obesity, which results in a greater rate of no-calls for obese pregnant women. Guidelines regarding NIPT in prenatal screening have been published, but with few and divergent recommendations on the issue.

[Androgen insensitivity syndrome discovered due to discordance in prenatal assessments of fetal gender].

In this case report, a pregnant woman chose non-invasive prenatal testing (NIPT) following a combined first-trimester screening showing a risk of trisomy 21 at 1:200. The NIPT was normal, and the sex of the fetus was predicted to be male. At 20 gestational weeks, an ultrasound examination predicted the fetus to be female.

A Novel Mutation of the Calcium-Sensing Receptor Gene Causing Familial Hypocalciuric Hypercalcemia Complicates Medical Followup after Roux-en-Y Gastric Bypass: A Case Report and a Summary of Mutations Found in the Same Hospital Laboratory.

Heterozygous inactivating mutations in the calcium-sensing receptor (CaSR) gene are known to cause familial hypocalciuric hypercalcemia (FHH), usually a benign form of hypercalcemia without symptoms of a disrupted calcium homeostasis. FHH can be mistaken for the more common primary hyperparathyroidism (PHPT), for which surgical treatment may be needed. We describe a case of a 36-year-old woman with hypercalcemia and elevated PTH, initially suspected of having PHPT.

Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting - factors of importance for correct interpretation of results.

Objectives: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity.

Study Design: This investigation is a retrospective case-control study performed in a public NIPT center.

Discordant non-invasive prenatal testing (NIPT) - a systematic review.

With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results.

[Non-invasive prenatal testing is a breakthrough in prenatal screening].

Non-invasive prenatal testing (NIPT) using cell-free fetal DNA from the peripheral blood of the pregnant woman has become a possibility within recent years, but is not yet implemented in Denmark. NIPT has proven to be very efficient in the screening for especially trisomi 21. This article summarizes the basics behinds the most used NIPT techniques and describes which genetic conditions this method may detect.

Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young.

Aims/hypothesis: Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY. Genomic deletions of the HNF1B (also known as TCF2) gene have recently been shown to account for one third of mutations causing renal cysts and diabetes syndrome. We investigated the prevalence of partial and whole gene deletions in UK patients meeting clinical criteria for GCK or HNF-1alpha/-4alpha MODY and in whom no mutation had been identified by sequence analysis.

Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits.

Aim: Recently, low-frequency polymorphisms in the coding region of the ghrelin gene were suggested to be involved in the aetiology of obesity and to modulate glucose-induced insulin secretion in different ethnic study groups. The objective of the present large study was to investigate whether the Leu72Met polymorphism of the ghrelin gene associates with features of the metabolic syndrome (MS) in the Danish population.

Methods: The variant was examined, using PCR-RFLP, in the DanMONICA cohort, a population-based sample of 2413 subjects.

Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome.

The peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1alpha is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies suggested linkage between the chromosomal region of PGC-1alpha and fasting serum insulin levels, and associates a Gly482Ser polymorphism of the gene with type 2 diabetes and hypertension.

Studies of variability in the islet amyloid polypeptide gene in relation to Type 2 diabetes.

Aims: To explore whether the coding region of the islet amyloid polypeptide (IAPP) gene contains genetic variants associated with Type 2 diabetes and whether a previously reported association of the promoter variant -132g-->a with Type 2 diabetes could be reproduced in Danish Caucasians.

Methods: The coding region was analyzed using single strand conformation polymorphism (SSCP) and heteroduplex analysis in 192 Type 2 diabetic patients. Restriction fragment length polymorphism (RFLP) was employed to screen for the promoter variant in 414 Type 2 diabetic patients and 182 glucose-tolerant control subjects.

Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.

Aims/hypothesis: We aimed to examine the promoter of SUR1 for genetic variation and to determine if variants were associated with Type II (non-insulin-dependent) diabetes mellitus or measures of beta-cell function.

Methods: We examined 465 bp upstream of the ATG site in 46 Type II diabetic patients and 15 glucose tolerant control subjects by SSCP-heteroduplex analysis.

Results: We identified an a --> t substitution 437 bp upstream of the ATG site.

Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity.

Aims/hypothesis: The aim of this study was to screen part of the putative promoter sequence in addition to 14 potential phosphotyrosine residues of human IRS-2 for genetic variability which might cause changes in protein expression or function. Furthermore, the potential impact on insulin secretion and sensitivity of a previously identified IRS-2 variant (Gly1057Asp) was analysed.

Methods: The screenings were carried out by the SSCP-heteroduplex technique on DNA from Type II (non-insulin-dependent) diabetic patients.

A novel Phe75fsdelT mutation in the hepatocyte nuclear factor-4alpha gene in a Danish pedigree with maturity-onset diabetes of the young.

Mutations in 5 different genes [the hepatocyte nuclear factor (HNF)-4alpha), glucokinase, HNF-1alpha, insulin promoter factor-1, and HNF-1beta genes] have been shown to cause maturity onset diabetes of the young (MODY). About 50% of all known MODY in Danish Caucasian MODY probands can be explained by mutations in the HNF-1alpha gene (MODY3). To estimate the prevalence of MODY caused by mutations in the HNF-4alpha gene (MODY1), we screened 10 non-MODY3 probands for mutations in the minimal promoter and the 12 exons of the HNF-4alpha gene.

Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells.

The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q.