Whole-exome sequencing reveals a gene mutation that comes into play only if inherited from the father.
For a small subset of boys and girls who undergo early puberty, there’s now a specific explanation. New genetic research, involving whole-exome sequencing, has identified four novel heterozygous mutations in a gene known as
MKRN3. Interestingly, while precocious puberty is more common in girls, all 15 affected children in the study inherited the mutations from their fathers.
Precocious puberty—the development of secondary sexual characteristics before 8 years in girls and 9 years in boys—has been associated with short stature, long-term health risks and an increase in conduct and behavioral disorders during adolescence. Physiologically, there are two types: central and peripheral. Central, the more common form, occurs when the pituitary gland, which controls puberty development, is activated too early.
“While a great deal of genetic studies have focused on the overall genetic contribution to pubertal timing, far less research has been conducted to find specific genetic causes of central precocious puberty,” says Andrew Dauber, MD, MMSc, of the Division of Endocrinology at Boston Children’s Hospital, who co-authored the study, published online this week by The New England Journal of Medicine. Full story »
In the developing world, health care providers often don’t have access to diagnostic technologies like the automated lab tests taken for granted in the resource-rich United States. Specimens often have to be sent to a distant central lab, and it can be weeks before an answer wends its way back.
That’s a tough situation when you’re, say, trying to assess whether a patient is having liver toxicity from a drug, such as drugs used to treat tuberculosis (TB) and HIV. By the time the results come back and indicate you need to stop or switch medications, the patient may be long gone, unable to travel back to the clinic.
For the past four years, Nira Pollock, MD, PhD, associate medical director of the Infectious Diseases Diagnostics Lab at Boston Children’s Hospital, has been working with Diagnostics For All (DFA), a nonprofit organization based in Cambridge, Mass., to develop and test a low-cost diagnostic device that works on the spot, involving just a finger-stick and a square of paper. The technology is all in the paper square—using wax printing and microfluidics techniques Full story »
Ed Smith explains the moyamoya operation during a live webcast.
Lindsay Hoshaw contributed to this post.
It’s 7 a.m. and neurosurgeon
Ed Smith, MD, is downing a Diet Coke as he reviews the MRIs of today’s patients. He sprints up a stairwell to greet his first patient in the pre-operating wing.
Thirteen-year-old Maribel Ramos, about to have brain surgery at Boston Children’s Hospital, sits in her bed fidgeting. Smith reassures her about the operation, promises they’ll shave off as little hair as possible, and gets Maribel to crack a smile by telling her he moonlights as a hairdresser. Full story »
As the close of American Heart Month draws near, let's take a moment to learn what two teams of scientists are doing to help heart transplant patients keep their new hearts in the long run. (englishsnow/Flickr)
You’re a heart transplant patient. You’ve been on the waiting list for months, maybe years. Now, you’re being wheeled out of the operating room, a donated heart beating in your chest.
You’ve finished one journey, but are only just starting on a new one: keeping your body from rejecting your new heart.
Luckily for you, new methods under development could help tell early on when chronic rejection problems—the kind that arise five or 10 years after your transplant—start to loom. And even better, scientists are homing in on a new way to prevent chronic (and maybe short-term) rejection from happening in the first place. Full story »
Just about any measurable molecule that changes with health and disease could be a biomarker. (David Guo's Master/Flickr)
Your doctor has a lot of tools to detect, diagnose and monitor disease: x-rays, MRIs, angiography, blood tests, biopsies…the list goes on.
What would be great would be the ability to test for disease in a way where there’s no or low pain (not invasive) and lots of gain (actionable data about the disease process itself, its progression and the success of treatment).
That’s where biomarkers come in. Full story »
In this family with 4 children with autism, genetic mapping and whole-exome sequencing identified a mutation in SYNE1, a gene that's known but never before associated with autism.
Autism clearly runs in some families, yet few inherited genetic causes have been found. A major reason is that these causes are so varied that it’s hard to find enough people with a given mutation to establish a clear pattern. Now, three large Middle Eastern families with autism spectrum disorders (ASDs) have led the way to a few more mutations, potentially broadening the number of genetic tests available to families.
What’s fascinating is that the mutations, described earlier this week in Neuron, affect genes known to cause severe, often lethal genetic syndromes. Milder mutations in the same genes, found through genomic sequencing, primarily cause autism.
Researchers Tim Yu, MD, PhD, Maria Chahrour, PhD, and senior investigator Christopher Walsh, MD, PhD, of Boston Children’s Hospital, started with three large families that had two or more children with an ASD, in which the parents were first cousins. Cousin marriages are a common tradition in the Middle East that greatly facilitates the identification of inherited mutations—as does large family size. Full story »
(Garry Knight/Flickr)
Vector has been deliberating about its predictions for 2013, consulting its many informants. Here’s where we’re putting our money this year; if you have other ideas, scroll to the bottom and let us know.
Genome sequencing scaling up at health care institutions
Last year we predicted genome sequencing’s entry into the clinic; this could be the year it goes viral. Technology companies with ever-faster sequencers and academic medical centers are teaming up at a brisk pace to offer genomic tests to patients. Just in the past two weeks, a deal was announced between The Children’s Hospital of Philadelphia and BGI-Shenzhen to sequence pediatric brain tumors; Partners HealthCare and Illumina Inc. announced a network of genomic testing laboratories; Full story »
A new spinoff business will make large-scale genomic diagnostics a reality in medical practice (Image: Rosendahl)
Genomic sequencing and molecular diagnostics are becoming a global business. At the recent American Society of Human Genetics meeting, dazzling technologies for reading genetic code were on display—promising faster, cheaper, sleeker.
Nevertheless, it’s become clear that the ability to determine someone’s DNA or RNA sequence doesn’t automatically translate into useful diagnostics or even actionable information. In fact, the findings are often confusing and hard to interpret, even by physicians.
That’s where academic-industry partnerships can flourish—tapping the deep expertise of medical research centers to bring clinical meaning to sequencing findings. Yesterday, Boston Children’s Hospital and Life Technologies Corp. announced a new venture with a great list of ingredients: fast, accurate, scalable sequencing technology—Life’s Ion Proton® Sequencer—but also research and clinical experience in rare and genetic diseases, bioinformatics expertise to handle the big data, and the medical and counseling expertise to create meaning from the results. Full story »
Mice with the mutation causing Rett syndrome (middle panel) have an excess of inhibitory connections as compared with normal mice (left panel) and mutated mice reared with no visual stimulation (right panel). Inhibitory connections were also reduced by manipulating the NMDA receptor, restoring a more normal balance of inhibition/excitation.
Research just published in Neuron offers some interesting clues about Rett syndrome, a tragic disease that causes initially healthy girls to lose their ability to speak and to develop motor and respiratory problems. Working with a mouse model, the Boston Children’s Hospital lab of Michela Fagiolini, PhD, explored how the causative mutations, affecting the MECP2 gene, disrupt brain circuitry and function. The team found that the circuit damage can be undone by targeting the NMDA receptor, tipping the brain toward the right balance of inhibition and excitation. They’re now exploring possible pharmaceutical approaches.
The study also suggests that changes in the visual system are a tip-off to what’s going on in the brain as a whole. Full story »
A “heat map” for autism gene expression (click to enlarge). Each row represents one of the 55 genes differently expressed in ASD patients vs. controls; columns show expression profiles for each of the 99 subjects. Genes in red have relatively increased gene activity; green, reduced activity. The bars along the bottom show how ASD patients vs. controls are distributed; overall, the ASD group has more genes over-expressed, while the control group has more down-regulated. The brackets at left connect genes that tend to be expressed together, while those along the top link individuals with similar gene expression patterns.
Though autism can respond well to early behavioral interventions, it’s typically not diagnosed in the U.S. until around age 5, when these interventions are less effective. Autism is diagnosed based on a child’s behaviors and language, which take time to develop to the point where clinicians can reliably assess them. What’s really needed is a fast, objective test when a child is much younger, before symptoms even show up.
In the past decade, researchers have chipped away at the problem, linking more than a dozen genetic mutations to autism—from small DNA “spelling” changes to lost or extra copies of a gene or genes (known as copy number variants) to wholesale chromosome abnormalities. Tests have been created, such as the chromosomal microarray test. But together, the known mutations account for, at best, 1 in 5 autism cases among tested patients. Full story »
