NIH Takes Aim At Fragile X Syndrome

The National Institutes of Health has developed a research plan to advance the understanding of fragile X syndrome and its associated conditions, fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Fragile X syndrome causes intellectual and developmental disabilities and results from a mutation in a gene on the X chromosome.

The plan puts forward goals to guide future research, setting research priorities for each of the conditions. One major priority of the plan is to investigate the biological processes underlying all three disorders, and how to better diagnose and treat them. Other priorities include studying how widespread the gene variations are in the population and investigating how the three conditions affect families.

Although the three disorders have very different symptoms, all result from variations in the same gene, known as the Fragile X Mental Retardation 1 (FMR1) gene. Full mutation of the gene means that cells do not produce a protein involved with communications between neurons in the central nervous system. The resulting disorder, Fragile X syndrome (FXS), occurs in approximately one in 2,500 births. People with FXS often have intellectual disabilities that range from mild to severe. They may also have emotional and behavioral problems, including attention problems, hyperactivity, anxiety, aggression, and autism or autism spectrum disorder.

People with a less dramatic change in the gene have what is called a pre-mutation, which increases their chance of having a child with FXS. These people may not have any apparent health problems or may have symptoms of Fragile X-associated tremor/ataxia syndrome or Fragile X-Associated Primary Ovarian Insufficiency.

To develop the plan, the NIH convened three working groups of experts, one for each of the conditions. Members of each group included experts from the scientific community, members of advocacy groups for individuals and their families affected by the disorders, and other federal agencies. The research plan identifies research goals for each of the three conditions, and outlines strategies for better diagnosis, treatment, and prevention of the three disorders.

The report also highlights ongoing research, including collaborative efforts from several NIH institutes: the NICHD, the National Institute of Neurological Disorders and Stroke, the National Institute of General Medical Sciences, the National Institute of Mental Health, and the National Institute on Aging. The NIH funds a network of centers devoted to Fragile X syndrome and its associated conditions, as well as studies by independent scientists. The release is available at http://www.nichd.nih.gov/publications/pubs_details.cfm?from=&pubs_id=5729.

Genetic Variant Linked to High BP in African-Americans

A team led by researchers from the National Institutes of Health reported the discovery last month of five genetic variants related to blood pressure in African-Americans…findings that may provide new clues to treating and preventing hypertension. The effort marks the first time that a relatively new research approach, called a genome-wide association study, has focused on blood pressure and hypertension in an African-American population. About one-third of US adults suffer from hypertension. The condition is considerably greater in the African-American community, in which the condition affects 39% of men and 43% of women.

To produce their findings, researchers analyzed DNA samples from 1,017 participants in the Howard University Family Study, a multigenerational study of families from the Washington, DC metropolitan area who identified themselves as African-American. Half of the volunteers had hypertension and half did not. To see if there were any genetic differences between the two groups, researchers scanned the volunteers’ DNA, or genomes, analyzing more than 800,000 genetic markers called single-nucleotide polymorphisms.

The researchers found five genetic variants significantly more often in people with hypertension than in those without the condition. The variants were associated with high systolic blood pressure, but not with diastolic blood pressure or combined systolic/diastolic blood pressure.

In May, two major international studies used the genome-wide association approach to identify 13 genetic variants associated with blood pressure and hypertension in people with primarily European and South Asian ancestry. While each variant was associated with only a slight increase in blood pressure, that work found that the more variants an individual had, the greater his or her risk of hypertension. Two genes identified by one of those studies were also associated with blood pressure in the new study.

The researchers found that all of the five genetic variants associated with blood pressure were located in or near genes that code for proteins thought to be biologically important in hypertension and blood pressure. Previous research had implicated two of those genes in blood pressure regulation, and additional analyses revealed that all of the variants are likely involved in biological pathways and networks related to blood pressure and hypertension.

An existing class of anti-hypertension drugs, called calcium channel blockers, already targets one of the genes, CACNA1H. However, the additional genes may point to new avenues for treatment and prevention.

To follow up and expand upon their findings in African-Americans, the researchers scanned DNA from 980 West Africans with and without hypertension. The work confirmed that some of the genetic variants detected in African-Americans were also associated with blood pressure in West Africans.

Transmission Pattern Discovery May Help Prevent Rotavirus Epidemics

New vaccines have the potential to prevent or temper epidemics of the childhood diarrhea-causing disease rotavirus, protect the unvaccinated, and raise the age at which the infection first appears in children, according to federal researchers in a study last month. The findings were based on changing patterns of rotavirus transmission in the United States, where the disease is rarely fatal, and they have implications for combating epidemics in other countries where the death toll is much higher.

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