A rare disease which often first presents in newborn babies has been traced to a novel genetic defect, scientists at Queen Mary, University of London have found.
The research, published online in Nature Genetics (27 May) discovered 20 distinct mutations in a specific gene found in patients with the rare adrenal disease, Familial Glucocorticoid Deficiency (FGD).
The potentially fatal disease means affected children are unable to produce a hormone called cortisol which is essential for the body to cope with stress.
Lead researcher Dr Lou Metherell*, endocrine geneticist at Queen Mary, University of London, said: "People who inherit this disease are unable to cope with physical stress.
For example, the normal response to infection or traumatic injury is to produce cortisol supporting the metabolic response to the event. Patients with FGD cannot do this and may die if untreated.
"We found 20 distinct defects in the antioxidant gene nicotinamide nucleotide transhydogenase (NNT) in patients from all over the world who suffer from FGD."
The researchers, which include Eirini Meimaridou and Professor Adrian Clark, also at Queen Mary in the William Harvey Research Institute, had previously found defects in four genes present in this disease.
The new research uncovered mutations in NNT, an antioxidant gene, which provides a new mechanism for this adrenal disease.
"Patients with this form of FGD exhibit oxidative stress (OS) in the adrenal, a process which is involved in other diseases such as neurodegenerative conditions, cancer, stroke, diabetes and cardiac dysfunction," Professor Clark said.
"If we can discover how the OS causes its effect then this might give us clues to the mechanism in other diseases like those listed above and it may then be possible to use appropriate drugs to reduce or prevent it."
More information: "Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency" was published online in Nature Genetics on 27 May 2012.
Stargardt disease is a rare yet life devastating condition. It is the most common form of inherited macular degeneration, and affects about one in 10,000 people (about 30,000 people in the United States).
There is currently no cure or treatment for Stargardt disease but clinical trials using gene and cell therapies are currently undergoing.
Patients with Stargardt most often start experiencing significant vision loss during their childhood and teenage years (60% of the patients are diagnosed before 20 years of age).
This vision loss cannot be corrected by glasses, and diagnosis had been traditionally delayed due to the young age of the patients and the rareness of the disease.
After diagnosis, and depending on age at onset, vision deteriorates progressively to levels below 20/200 (legal blindness).
The disease affects mostly the central vision and spares some of the peripheral vision, although there are very severe forms that lead to complete blindness.
Almost all of those affected by Stargardt disease will live legally blind during their adult lives, although patients with late onset may retain some visual acuity.
Loss of central vision leads to impossibility to perform tasks such as reading, writing, driving or recognizing faces.
In 1997, scientists discovered that Stargardt disease results from a defective gene, the ABCA4, responsible for the synthesis of an important protein called Rim protein.
A normally functioning Rim protein transports vitamin A molecules from the photoreceptors (the molecules sensitive to light) back into specialized cells (called RPE), where vitamin A molecules are recycled to be reused for vision.
In Stargardt, the defects in the ABCA4 gene lead to partial or full dysfunction of this protein. As a result, vitamin A transport is affected and vitamin A molecules tend to accumulate in the photoreceptors.
This accumulation leads to the formation of toxic pigments (known as "vitamin A dimers") believed to be partly responsible for vision loss.
Although normal individual also form vitamin A dimers, this process usually takes decades, explaining why age-related macular degeneration (AMD) occurs later in life of normal people, while the same process takes only a few years in Stargardt explaining vision loss from childhood.
Celebs the boys wrote to included David Cameron, ITV presenter Lorraine Kelly, The Duchess of Cambridge, Bill Gates, Daniel Radcliffe and children’s laureate Julia Donaldson and the youngsters have been lucky enough to receive responses from all of the above.
Director at the charity, Michael Lewington, said it was fantastic to know Audio Calibre, which sends out around 1,800 audio books a day, has been able to help the boys so significantly.
“The fact that the two boys decided to write all those letters is wonderful – and it’s so heart-warming that celebrities such as Lorraine Kelly could find the time to respond with handwritten letters.
“They even received a response from Downing Street and the royals, who must get thousands and thousands of letters.
“All of this has of course really done well to raise the profile of the charity, and as the boys are from Scotland, it’s raised our profile there, too. It’s all about letting people know we’re out there.
“The aim of the charity is to provide audio books to anyone who is ‘print disabled’, which means that as a result of dyslexia or physical disabilities, they are unable to read books.
“We have around 18,500 members, and more than half of our children are dyslexic.
“As a director here, I actually feel like I can personally give back to the community.
“Audio books can be of so much benefit to kids – it’s been proven that it actually improves their academic progress, as well as their general wellbeing. And with older people, who perhaps cannot hold a book because of sever rheumatoid arthritis, it allows them to start reading again.”
Pupils kept out of formal schooling until the age of seven perform just as well those subjected to normal lessons at five, it was revealed.
In some assessments of reading skills, those with a later start actually overtook their peers by the age of 10, figures show.
Academics suggested that infants given more time to naturally develop their language skills in the early years had a better foundation when they started conventional tuition at seven.
The disclosure – based on an analysis of pupils in New Zealand – will raise fresh concerns over Government reforms to pre-school education which appear to place a greater focus on the three-Rs at an increasingly early age.
This includes subjecting all pupils to a new-style reading test at six to identify those lagging behind.
It comes after a major US study showed that bright children actually benefited from being slowed down in the early years, suggesting that they risked growing up in an “intellectually unbalanced” way by being pushed too far, too soon.
Most British schoolchildren already start classes earlier than their peers in many other European nations. Children are normally expected to be in lessons by five, although most are enrolled in reception classes aged four.
But the latest study – published in the journal Early Childhood Research Quarterly – found that children who begin decoding words later than their peers can “eventually achieve equally in reading fluency”.
“Our findings suggest that success at reading is not assured by an earlier beginning,” it said.
Academics from Regensburg University in Germany and Otago University in New Zealand tracked hundreds of children who started formal schooling at different ages.
This includes those who joined conventional New Zealand state schools at five and others from progressive Steiner schools, who are allowed to delay formal tuition until seven.
The second group remained in Steiner nurseries for two more years, where written language is banned to encourage the development of oral communication and children spend time on play-based activities, such as painting, drawing, cooking, singing or oral storytelling, the study said.
Children were given reading tests at different stages during the first six years of their primary education to assess their ability to decode individual words and fluently read a passage of text.
The study, led by Dr Sebastian Suggate, found that those learning to read later had caught up by the age of 10 and actually had “slightly better reading comprehension” before the end of primary education.
“Instead of focusing on developing decoding-related skills between the ages of five and seven, and in the first years of school, it may be that the environments in the Steiner kindergartens favoured language development, which later feeds into reading comprehension,” said the research.
The findings come amid claims from academics that children in England are being pushed too hard at a young age.
Currently, all nurseries and childminders are expected to follow a compulsory pre-school curriculum that requires children to hit a series of targets before their fifth birthday.
This includes reading and understanding simple sentences in books, writing simple sentences, counting up to 20, using simple addition and subtraction and employing everyday language to describe and compare size, weight, capacity, time and distance.
Several years after launching its online one-on-one brain-training program that treats people with learning disabilties and concentration problems, Brain Potential Institute claims it has affirmative evidence that the program is equally as successful when completed online as at its onsite center.
The Institute believes that Results of the online treatment program indicate a significant increase in IQ, attention, focusing, and memory for those with ADD, ADHD, central auditory processing issues, autism and memory loss.
Jane Davis, P.T., M.S.H.P founded Brain Potential Institute in 2002 as Kid Potential Inc. The company expanded its services to provide brain training to teens, adults and seniors, which required rebranding itself as Brain Potential Institute.
Brain Potential Institute is dedicated to optimizing through cognitive training, the human brain to reach its highest intellectual potential for optimum performance at school and work, and to preserve brain function at all ages. Brain Potential Institute accepts students ages 3 through 90. Screenings are free
Brain Potential Institute claims to be one of the few companies able to increase a persons IQ by significant numbers. Its program is aimed to help with concentration issues, math and reading problems, development disorders and a litany of other cognitive and learning disabilities.
The foundation on which Brain Potential Institute has based its program is neurogenesis the brains ability to create new neuro-pathways.
Jane Davis, P.T., M.S.H.P, CEO and founder, Brain Potential Institute states that many students have gained three grade levels in reading and experienced up to a 30-point IQ increase.
The Reading Focus Card can help children and adults, especially those with ADD, ADHD & dyslexia, read more easily. It is non-invasive with no side effects because no medication is involved.
Dubbed the “Goldilocks effect” by the University of Rochester team that discovered it, the attention pattern sheds light on how babies learn to make sense of a world full of complex sights, sounds, and movements.
The findings could have broad implications for human learning at all ages and could lead to tools for earlier diagnosis of attention-related disabilities such as ADHD or autism, says Celeste Kidd, lead author on the paper published in the journal PLoS ONE and a doctoral candidate in brain and cognitive sciences.
With the aid of eye-tracking devices and statistical modeling, the research is the first to provide both a theory and quantifiable measures of what keeps a baby’s attention, says study co-author Richard Aslin, a professor of brain and cognitive science.
For years, researchers have explored what types of events most effectively capture babies’ attention. In some situations, infants reliably prefer familiar items, such as a favorite toy; in others, they favor novel objects.
The new study resolves such seeming contradictions. Instead of novelty or familiarity per se, the research shows that babies seek out situations with just the right amount of surprise or complexity.
Surprise!
To measure complexity, the team developed a test based on the probability of surprising events in a video.
Unlike hard-to-quantify concepts such as novelty or unlimited dimensions such as size, probability exists in a well-defined range from 0 (never happens) to 1 (always happens). Probability provides a continuous measure and is often employed by computer scientists and engineers to describe complexity, says Aslin.
In the study, researchers measured the attention patterns of 72 seven- and eight-month-old infants in two separate experiments. The babies watched video animations of fun items, such as a pacifier or ball, being revealed from behind a set of colorful boxes. The researchers varied where and when the objects would appear across dozens of short trials.
To measure attention, an eye-tracking device located below the computer screen followed the infants’ gaze. As long as they looked at the screen, the events continued; as soon as they looked away, the trial ended.
Babies quickly learned that they were in control. If they wanted to continue watching they just needed to keep their eyes on the screen. To reduce distractions, infants sat in a darkened space on the lap of their parent, who wore headphones playing music and a visor to prevent them from biasing their infant’s performance.
‘Not passive sponges’
Using a specialized statistical model, the researchers were able to calculate and predict how likely infants were to lose interest based on the complexity of each event depicted in the video. Complexity was defined as how surprising each event was in light of the previous events an infant had observed in the video.
Across both experiments, babies reliably lost interest when the video became too predictable—when the probability of a subsequent event was very high. “But here’s the counterintuitive part,” says Aslin. “You would think that the more complex something is, the more interesting it would be. That’s not the case with babies.”
They drifted away from the screen when the sequence of events also became too surprising—when the pattern seemed random and unpredictable because the probability of something happening was very low.
“The study suggests that babies are not only attracted by what is happening, but they are able to predict what happens next based on what they have already observed,” says Kidd. “They are not passive sponges.
They are active information seekers looking for the best information they can find.”
Although the experiments were limited to infants, the results provide a window into the way the brain works in general. “If you are interested in human nature, then babies are the place to look,” because their reactions are less complicated by cultural filters and learned responses, says Steven Piantadosi, a co-author and post-doctoral fellow in brain and cognitive sciences.
For example, the “Goldilocks” attention pattern supports other theories of adult learning, the authors note.
Cognitive scientists have proposed that learners direct their attention to material that contains just the right amount of challenge, because this optimal complexity triggers the right amount of stimulation in learners.
In real life, babies are also attracted to faces, voices, foods, and other aspects of their world that are key to survival. These “special” stimuli may trigger attention in a different way, the authors acknowledge. But complexity does help to explain how infants gather information about the rest of their environment, they write.
Advice for parents
Does this mean that parents should worry about providing material that is “just right” for their little ones?
Not really, says Aslin. “Infants are learning all the time, as long as they have reasonably stimulating environments. They focus in on what they can handle and filter out the rest,” he says.
Kidd agrees: “Parents don’t need to buy fancy toys to help their children learn. They make the best use of their environment. They are going to look around for what fits their attention level.”
And even though the experiment employed an animated video, the scientists emphasize that human interactions are the most critical for development. “Kids learn best from social interaction,” reminds Kidd.
The study’s insights into attention patterns may help to explain why children ask to hear the same story over and over. For an adult, the repetition can be mind numbing, says Kidd, “but for a child, they are likely getting something new out of the story every time. Because adults know so much, we often take for granted how many new things an infant needs to learn.”
The research was funded by a grant from the National Institutes of Health and the J. S. McDonnell Foundation.
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