Researchers at the University of Helsinki have found a genetic variation, which associates with the damage caused by maternal alcohol consumption. This genetic variation clarifies the role of genetic factors in the alcohol-induced developmental disorders and could be useful in future diagnostics.
The effects of prenatal alcohol exposure (PAE) on placental genes involved in growth and on the size of affected newborns were explored in the study performed at the University of Helsinki and Helsinki University Hospital in Finland. The researchers observed that alcohol alters epigenetic marks on the placenta and also the head size of newborn, depending on the genetic variation inherited from the parents.
Epigenetic marks are molecules, which bind to DNA sequence. They regulate the activity of genes and thus production of proteins in the cells.
The research material was 39 alcohol-exposed and 100 control placentas. They were collected from mothers who gave birth in the Helsinki University Hospital and had given approval for their participation in the study.
It is already known that in addition to neuronal disorders and birth defects, alcohol causes retarded growth. Therefore the researchers focused on two genes, insulin-like growth hormone 2 (IGF2) and H19, which locate near each other and regulate the growth of the placenta and embryo.
There is a common genetic variation in the Finnish population in the DNA region which regulates the function of these genes. The genetic variants that an individual inherits from the parents have been shown to associate with the amount of epigenetic marks on this region. This led the researchers to examine this intensively studied genomic region in a novel way.
– We divided all our samples in four groups according to the inherited genetic variations. We observed that there were different quantities of epigenetic marks in the groups of alcohol-exposed placentas compared with controls, explains Adjunct Professor Nina Kaminen-Ahola, the leader of the research team at the University of Helsinki.
– This finding led us to explore if there are changes in the gene expression and newborns’ birth measurements that would associate with the variation. We observed that expression of the negative growth controller H19 was significantly increased compared to expression of the growth supporter IGF2 in certain variant groups of the alcohol-exposed placentas.
The birth measurements were analysed by using new Finnish growth charts. Previous studies have shown that alcohol particularly affects the head growth and thus head circumference has been used as a mark of alcohol-induced damage. However, this study indicated that the head circumferences of alcohol-exposed newborns vary significantly depending on the genetic variations inherited from parents.
– We do not know yet if this variation is connected with alcohol-induced neuronal disorders. However, this could explain earlier study results concerning decreased correlation between HCs and brain size, as well as between HCs and cognitive skills among alcohol-exposed children. This suggests that alcohol causes damage in the brain in all genotypes, but this cannot be always seen in the head size, Kaminen-Ahola states.

University of Helsinki
www.helsinki.fi/en/news/a-candidate-genetic-factor-for-the-effects-of-prenatal-alcohol-exposure-has-been-found

Ortho Clinical Diagnostics (Ortho) and EKF Diagnostics (EKF) recently announced an agreement that allows Ortho customers to access EKF’s Stanbio Chemistry Beta-Hydroxybutyrate (BHB) LiquiColor^® assay. This is an important marker used in conjunction with clinical findings and other lab tests for the diagnosis and management of ketoacidosis and its main causative factor, diabetic ketoacidosis (DKA). The high-quality, fully automated assay is now available for use on Ortho’s VITROS^® 4600 Chemistry System and the VITROS^® 5600 Integrated System.

Diabetic ketoacidosis is a serious complication that can lead to a disruption of chemical balance in the body, and can be fatal if left undiagnosed. EKF’s enzymatic Beta-Hydroxybutyrate (BHB) assay is used primarily for determining both the presence and degree of ketosis in suspected diabetic ketoacidosis cases. The BHB assay produces a quantitative value that is specific to the BHB ‘ketone body’. These qualities make the BHB assay the new clinical diagnostic standard of care for ketone testing.

“Ortho is committed to delivering a broad menu of assays to our customers in the clinical lab, whether through in-house development or collaborations like the one with EKF,” said Ortho’s chief Operating Officer Robert Yates.

Ortho and EKF are collaborating to provide the BHB assay as a validated MicroTip Partnership Assay (MPA) application in the U.S. and Canada. This MPA utilizes the User Defined Assay (UDA) feature, which provides the capability to program assay parameters as defined in the EKF Stanbio Assay Application Sheet. The Beta-Hydroxybutyrate LiquiColor^® assay has been CLIA classified by the U.S. Food and Drug Administration (FDA) as a MODERATE complexity assay on the VITROS^® 4600 Chemistry System and VITROS^® 5600 Integrated System.

“Diabetic ketoacidosis is a serious condition, and our collaboration with Ortho Clinical Diagnostics will help to deliver the important BHB assay to their existing customers” said EKF’s Diagnostics Head of Sales, Gilbert Mejia.

EKF Diagnostics’ Stanbio Chemistry portfolio is a broad range of liquid-stable reagents, calibrators, standards and controls. LiquiColor^® and Liqui-UV^® reagents are designed for maximum stability, ease-of-use and are optimized for today’s chemistry analyzers. In addition to its BHB test for ketosis, EKF continues to build on its successful range of esoteric reagents.

Rare variants combined with background genetic risk factors may account for many unexplained cases of familial breast cancer, and knowing the specific genes involved could inform choice of prevention and treatment strategies.
Researchers Na Li, MD, Ian Campbell, PhD, lead investigator; and their colleagues at the Peter MacCallum Cancer Centre in Melbourne, Australia, focused their study on patients at high risk of breast cancer: those with a personal or family history who were seeking an explanation.
“When you know which gene is conferring the risk of breast cancer, you can provide a more precise estimate of risk, know what to expect and watch out for, and tailor risk management strategies to the patient,” said Dr. Campbell. Unfortunately, in about half of these high-risk patients, no known genetic cause was found, suggesting a more complicated explanation. In such cases, cancer geneticists had long suspected that polygenic risk (risk conferred by a combination of genetic variants) was involved.
Genes do not work on their own, but rather as part of one’s overall genetic context, explained Dr. Li. “That ‘polygenic risk’ background is like a landscape full of hills and valleys, with each risky variant like a house on top of it,” she said. “If you inherit a high-risk variant – a tall house – but live in a valley, your overall risk of breast cancer may end up being average because your genetic landscape pulls it down.”
The concept of background genetic risk is not new, but for many years, scientists did not have the tools to collect and analyse the thousands of genomes needed to quantify it. Recent improvements in next-generation sequencing technology have addressed this challenge. As a result, Dr. Li and colleagues were able to sequence up to 1,400 candidate breast cancer genes in 6,000 familial breast cancer patients and 6,000 cancer-free controls. In this large sample, they searched for potential cancer-associated genes suggested by the literature, collaborators, and their own previous results, and identified at least 46 genes that were at least twice as likely to have mutations among participants with breast cancer than in those without.
They also used the data to calculate a polygenic risk score for each patient, and combined this score with data on their high and moderate-risk variants to estimate each patient’s overall risk of developing breast cancer. In the coming years, the researchers plan to expand the study internationally to further test and refine their findings across populations. They also hope to bring these more precise risk estimates into the clinic, to more accurately reassure women about their personal risk of cancer, or – if risk is high – advise preventive strategies such as screening at a younger age.

American Society of Human Genetics
www.ashg.org/press/201710-breast-cancer.shtml

Children who are considered to be at risk of developing eye cancer should receive genetic counselling and testing as soon as possible to clarify risk for the disease. This is the consensus of leading ophthalmologists, pathologists and geneticists, who worked for two years to develop the first U.S. guidelines on how to screen for the most common eye tumour affecting children. The goal is to ensure retinoblastoma is detected at the earliest possible stage so ophthalmologists can save the lives and vision of more children.
Retinoblastoma is a cancer that starts in the retina, the very back of the eye. It can also spread to other parts of the body, including the brain and bones. There are approximately 350 new cases diagnosed each year in the United States.
The disease primarily affects young children. It can be either hereditary or non-hereditary. Children with hereditary retinoblastoma often develop retinal tumours in both eyes within the first years of life. Early diagnosis, when tumours are small, improves the child’s chance of survival and their chance of keeping their vision and their eyes.
Development of these guidelines began when ophthalmologist Alison Skalet, M.D., Ph.D., of the Casey Eye Institute in Portland, Ore., searched for an optimal screening strategy for her own patients and found little published guidance.
For the next two years, Dr. Skalet and Patricia Chévez-Barrios, M.D., ophthalmologist, and pathologist from Houston Methodist Hospital, led members of the American Association of Ophthalmic Oncologists and Pathologists, and a team of experts to devise guidelines. The effort was also supported by the American Association for Pediatric Ophthalmology and Strabismus, the American Academy of Ophthalmology, and the American Academy of Pediatrics.
The guidelines address a knowledge gap among ophthalmologists and other health care professionals in the U.S. regarding risk for inherited retinoblastoma and best practices for screening examinations. It is anticipated that they will also influence care in other countries. Therefore, the guidelines were written to provide a general framework for care that can be modified based on local resources, and provider and parental preferences. The recommendations acknowledge paediatric anaesthesia and genetic testing may be limited in many developing countries, preventing strict adherence. So, the guidelines offer direction in cases when these resources are unavailable.
Dr. Chévez-Barrios said the new guidelines meet the team’s goal to focus care on children at the highest risk for disease while decreasing unnecessary examinations for children at lower or no risk of developing retinoblastoma.
“We wanted to make sure all the doctors who come in contact with these patients are aware of how to diagnose and treat them so we can save more eyes, more vision and of course more lives,” said Dr. Chévez-Barrios.
Ophthalmologists say there are signs to look for that may indicate retinoblastoma. They include a white colour in the pupil when a light is shone in the eye, such as when taking a flash photograph. Also, eyes that appear to be looking in different directions could be a sign of trouble. They encourage parents to make an appointment with their child’s paediatrician if they notice any changes to their child’s eyes.

American Academy of Ophthalmology
www.aao.org/newsroom/news-releases/detail/genetic-testing-for-children-at-risk-of-eye-cancer