Thursday, May 31, 2012

The Same Gene That Makes Kids Grow Too Fast Can Also Cause Stunted Growth

UCLA geneticists have identified the mutation responsible for IMAGe syndrome, a rare disorder that stunts infants' growth. The twist? The mutation occurs on the same gene that causes Beckwith-Wiedemann syndrome, which makes cells grow too fast, leading to very large children. Published in the journal Nature Genetics, the UCLA findings could lead to new ways of blocking the rapid cell division that allows tumors to grow unchecked. 

The discovery also offers a new tool for diagnosing children with IMAGe syndrome, which until now has been difficult to identify accurately. The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor of human genetics, pediatrics and urology at the David Geffen School of Medicine at UCLA. Nearly 20 years ago, as a medical resident in his native France, Vilain cared for two boys, ages 3 and 6, who were dramatically short for their ages. 

Though unrelated, the children shared a mysterious malady marked by minimal fetal development, stunted bone growth, sluggish adrenal glands, and undersized organs and genitals. "I never found a reason to explain these patients' unusual set of symptoms," said Vilain, who also directs the UCLA Institute for Society and Genetics. 

"I've been searching for the cause of their disease since 1993." When Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. His UCLA mentor at the time, geneticist Dr. Edward McCabe, recalled a similar case from his previous post at Baylor College of Medicine. The two of them obtained blood samples from the three cases and analyzed the patients' DNA for mutations in suspect genes but uncovered nothing. 

 Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism and in 1999 published the first description of the syndrome, which they dubbed IMAGe, an acronym of sorts for the condition's symptoms: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia and genital anomalies. 

 Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery. Help arrived unexpectedly last year, when Vilain received an email from Argentinian physician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilain about a large family he was treating in which eight members suffered the same symptoms described in the study.

 All of the family members agreed to send their DNA samples to UCLA for study. Vilain realized that he had stumbled across the scientific equivalent of winning the lottery. He assembled a team of UCLA researchers to partner with Bergada and London endocrinologist Dr. John Achermann. "At last, we had enough samples to help us zero in on the gene responsible for the syndrome," Vilain said. "Sequencing technology had also advanced in sophistication over the past two decades, allowing us to quickly analyze the entire family's DNA samples." 

 Vilain's team performed a linkage study, which identifies disease-related genetic markers passed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11. The UCLA Clinical Genomics Center performed next-generation sequencing, a powerful new technique that enabled the scientists to scour the enormous area in just two weeks and tease out a slender stretch that held the culprit mutation.

 The team also uncovered the same mutation in the original three cases described by Vilain and McCabe in 1999. A word of explanation: Located on 23 pairs of chromosomes, human genes hold the codes for making cellular proteins, the building blocks for our bodies. Most of the human diseases resulting from mutations in a single gene can be blamed on changes in a protein-coding sequence. By scanning the entire exome, or protein-coding factory of the genome, clinical geneticists can interpret every gene variant to track down the mutations that produce a patient's disease and rapidly reach a clear-cut diagnosis.

 UCLA is one of only three academic centers in the nation that offers next-generation sequencing to the public for clinical use. "We discovered a mutation in a tiny sliver of the chromosome that appeared in every family member affected by IMAGe syndrome," Vilain said. "This was a big step forward. Now we can use gene sequencing as a tool to screen for the disease and diagnose children early enough for them to benefit from medical intervention.

 "We were a little surprised, because the mutation was located on a famous gene recognized for causing Beckwith-Wiedemann syndrome," he added. "The two diseases are polar opposites of each other." Children born with Beckwith-Wiedemann syndrome - named for the two doctors who discovered it - grow very large, with big adrenal glands, elongated bones and oversized internal organs. Because their cells grow so fast, one in five children with the disorder die of cancer at a young age. 

The disease appears in approximately one out of 15,000 births. "Finding opposite functions in the same gene is a rare biological phenomenon," Vilain emphasized. "When the mutation appeared in the slim section we identified, the infant developed IMAGe syndrome. If the mutation fell anywhere else in the gene, the child was born with Beckwith-Wiedemann. That's really quite remarkable." IMAGe syndrome patients also tend to die young, due to poor adrenal activity, which physicians treat with hormone-replacement therapy.

 The findings proved that Vilain and his colleagues had identified the correct mutation, bringing his 20-year odyssey to a successful end. "Our findings leave no doubt that this set of symptoms is a true syndrome and not just a figment of my imagination," Vilain said. "What makes this special for me is finally being able to unravel what caused the life-threatening disease in the two patients I saw nearly 20 years ago," he added. "As a clinical scientist, the reward for successful research is uncovering new clues that allow us to help patients feel better by improving their medical care."

Exercise May Be Bad For Some

A new study suggests that not every healthy person benefits from regular exercise: for a small 7% minority it may increase heart and diabetes risk factors. The researchers did not suggest this should stop people exercising but point to the importance of using this type of knowledge to personalize exercise programs. 

 Claude Bouchard, a professor of genetics and nutrition in the Human Genomics Laboratory at Pennington Biomedical Research Center, Baton Rouge, Louisiana, in the US, was lead author of the study, which was published online in PLoS ONE on 30 May. Bouchard and colleagues write in their background information that public health guidelines suggest adults should do 150 minutes a week of moderate intensity physical activity, or 75 minutes a week of vigorous intensity activity. 

 However, it is now well established that different people respond differently to exercise in terms of cardiorespiratory fitness and cardiometabolic and diabetes risk factors. But the question that still remains, is whether there are people for whom the effect of regular exercise on these risk factors could be harmful. For their study, Bouchard and colleagues analyzed data from six rigorous studies that looked at the effect of exercise in a total of 1,687 adults. 

 These studies were the HERITAGE Family Study, the DREW Study, the INFLAME Study, and the STRRIDE Study, plus cohorts from two other studies, one from the University of Maryland and another from the University of Jyvaskyla. They looked to see how many of the participants experienced an adverse response to exercise, which they defined as an "exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation".

 Bouchard and colleagues produced their own parameters for this definition by measuring resting systolic blood pressure (SBP), fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) in 60 people over a period of three weeks.

Wednesday, May 2, 2012

Teenager, 19, who thought her watery eye was caused by make-up discovers it is CANCER tumour behind her nose



When Tasha Jilka began suffering from a watery left eye, she put the strange symptom down to her make-up or the seasonal weather.

But far from being an innocuous allergic reaction to cosmetics, the teenager's bizarre ailment was one which changed her life forever, as she was later diagnosed with cancer.

The 19-year-old's watery eye was caused by a rare cancer tumour called olfactory neuroblastoma at the back of her nose which left doctors eventually having to rebuild her whole face.

Tasha's rare diagnosis was eventually made a year after she first suffered the watery eye, having been missed by doctors and opticians.

Her ordeal began in May 2008, when, aged 16, her symptoms began.

Tasha, from Leicester, said: 'My left eye was very watery but I just put it down to make-up. It kept getting worse and I decided to go to my GP.

'It was put down to a cold and the weather and I was told it would go by itself.

'I went back a few times when it didn’t get better and was referred to an optician, but they couldn’t find anything either.'

Four months later, her eye had got worse and she was referred to a Cambridgeshire hospital, as she was living near there at the time.

Tasha had an operation to clear a blocked tear duct - but it still did not solve her problems.
In 2009, when she and her family moved to Leicester, she again went to her doctor and was referred to specialists at Leicester Royal Infirmary.

Tasha said: 'I had a similar eye test but this time doctors also looked up my nose and could see a lump.'

A biopsy was taken and a short time later, Tasha’s cancer was diagnosed.

She said: 'When I was told it was as if they were talking about someone else. I knew it was serious.

'I thought it was a little lump in my face but the news began to sink in.'

In May 2010 Tasha had surgery to remove the tumour.

It was so severe that surgeons had to reconstruct her nose and she is still having problems with the vision in one eye.




Nigeria has highest malaria cases in the world

The Minister of Health, Professor Onyebuchi Chukwu, has dislosed that Nigeria has the highest malaria cases in the world, adding that the country alone contributes 23 per cent, which is almost a quarter of the global malaria cases. 

 Chukwu, who was represented by Mrs Fatima Bamidele, Permanent Secretary, Federal Ministry of Health, stated this in Lagos, on Monday, at a dinner organised to mark the World Malaria Day, also disclosed that the country contributed about 11 per cent of maternal deaths and 30 per cent of child deaths, adding that 47 per cent of the global malaria burden came from just five countries, of which Nigeria is one.

 He said the country had been making efforts to contain the scourge through measures such as massive distribution of long lasting insecticide-treated nets, saying 46.8 million nets had been distributed so far in 30 states of the country. 

 Other measures taken to combat malaria, according to him, included scaling up in the use of indoor residual spraying (IRS) and larviciding; massive distribution of anti-malarial medicines and commodities; capacity building for health workers at both national and states’ levels and the establishment of effective coordination structures at national and states level.

 According to him, the Malaria Household Survey conducted in 2010 in nine states of Kano, Jigawa, Bauchi, Gombe, Kaduna, Anambra, Delta, Akwa Ibom and Rivers revealed an increase in the percentage of households with at least one insecticide treated net (ITN) from 2.2 per cent to 88 per cent. “There is also an increase in the percentage of children under five years of age who slept under nets the night preceding the survey from 3 per cent to 44.6 per cent,” he added.

 
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