Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome.

Purpose: Universal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database.

Methods: All patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included.

A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease.

Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidase's main subunit (gp91) and results in CGD. Analyzing two brothers diagnosed with CGD we identify a homozygous loss-of-function mutation, p.

COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA.

Background: Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance.

Case Presentation: Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population.

Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

Background: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B).

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.

Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory.

Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia.

In humans, the elucidation of the genetics underlying multifactorial diseases such as pre-eclampsia remains complex. Given the current day availability of genome-wide linkage- and expression data pools, we applied pathway-guided genome-wide meta-analysis guided by the premise that the functional network underlying these multifactorial syndromes is under selective genetic pressure. This approach drastically reduced the genomic region of interest, i.

Iceland-genetic counseling services.

This brief report aims to give an overview of the history and current status of clinical genetics services in Iceland and specific genetic counseling considerations for Iceland's population. Presently, there are two part time medical geneticists and one full time genetic counselor with an MSc education from Cardiff, within the Department of Genetic and Molecular Medicine, based in Iceland's only tertiary healthcare facility, Landspitali, the National University Hospital. An oncologist (20 %) also contributes to the cancer genetic counseling service.

Association of Morbus Ledderhose with Dupuytren's contracture.

Background: Fibromatous nodules in the sole of the foot are often called Ledderhose disease. It is a benign nodular formation in the plantar aponeurosis, typically at the distal medial border. A lump forms and it can be a few centimeters in diameter.

Association of HLA-DRB1*01 with Dupuytren's disease.

Objectives: To explore the human leucocyte antigen (HLA)-DRB1 allele frequency in Dupuytren's disease (DD).

Method: HLA-DRB1 genotypes were analysed by sequence-specific primers (SSPs) in samples collected from 172 men participating in a nested case-control study on the clinical manifestations and progression of DD. Of those, 121 had signs of DD while 51 did not.

Ichthyosis prematurity syndrome with separation of fetal membranes and neonatal asphyxia.

Ichthyosis prematurity syndrome (IPS) is a rare inherited skin disorder. Children are born prematurely with thick skin and have been found to develop neonatal asphyxia due to occlusions in the bronchial tree from debris in the amniotic fluid. At 31 weeks of gestation, separation of amniotic and chorionic membranes was identified as well as polyhydramnion.

[Ehlers-Danlos syndrome type IV. Case study and clinical findings].

We describe Ehlers-Danlos syndrome type IV in adult patients with a confirmed diagnosis and a systematic review of expected clinical findings in the disease. Serious complications were found in four individuals, two with gastrointestinal perforation at the age of 32 years, two had died from an aortic rupture (34 and 44 years old) and one has been diagnosed with aortic root dilatation. Most had also less severe clinical features such as varicose veins, easy bruising, thin and translucent skin, chronic joint subluxation or dislocation or pes planus.

C-reactive protein is elevated 30 years after eclamptic pregnancy.

Women with a history of preeclampsia or eclampsia (seizure during preeclamptic pregnancy) are at increased risk for cardiovascular disease after pregnancy for reasons that remain unclear. Prospective studies during pregnancy suggest that inflammation, dyslipidemia, and insulin resistance are associated with increased risk of preeclampsia. Elevated serum C-reactive protein (CRP >3 mg/L) is an indicator of inflammation and cardiovascular risk.

[Folic acid consumption by pregnant women prior to and during pregnancy.].

Objective: To study consumption of folic acid supplements by women before conception and during pregnancy. Concurrently, the incidence of planned pregnancy and the women's knowledge of the preventive value of folic acid was investigated.

Material And Methods: A questionnaire was presented to all 128 pregnant women attending a maternal clinic in rural area during one month's period.

Cardiovascular death in women who had hypertension in pregnancy: a case-control study.

Objective: To determine whether an association exists between hypertension in pregnancy and later development of cardiovascular disease.

Design: Case-control study of women who delivered with and without hypertensive complications during the same period.

Setting: University Hospital in Reykjavik, Iceland.

Searching for preeclampsia genes: the current position.

Although there is substantial evidence that preeclampsia has a genetic background, the complexity of the processes involved and the fact that preeclampsia is a maternal-fetal phenomenon does not make the search for the molecular basis of preeclampsia genes easy. It is possible that the single phenotype 'preeclampsia' in fact should be divided into different sub-groups on genetic or biochemical level. In the present review, the preeclampsia phenotype and its pathophysiologic features are discussed.