Team discovers genetic cause of rare high blood pressure syndrome

February 6, 2018, Berlin Institute of Health
Team discovers genetic cause of rare high blood pressure syndrome
Credit: Berlin Institute of Health

Twenty-five years ago, an unusual inherited form of high blood pressure was first described in an Australian family. Its genetic cause, however, had remained elusive. Using modern sequencing methods, an international research team led by BIH Johanna Quandt Professor Ute Scholl has succeeded in detecting mutations in a new disease gene (CLCN2)—present in this family and seven others—that are responsible for the development of a familial form of hyperaldosteronism.

More than a billion people worldwide suffer from high (hypertension). Prolonged hypertension damages blood vessels, which can result in damage to the heart, kidneys, and brain. Possible consequences include heart attack, kidney failure and stroke. Besides such factors as obesity, salt consumption, and alcohol intake, genetic factors play an important role in the development of hypertension. In some rare cases, familial hypertension is caused by mutations within single genes. These play important roles in blood pressure determination, and mutations typically cause early-onset hypertension, even in young children and adolescents. Ute Scholl and a team of scientists from the United States and Australia have now identified a new hypertension disease gene. The study focused on a particular and very rare form of high blood pressure, known as familial hyperaldosteronism type II. This inherited disease causes the to produce too much aldosterone—a hormone that regulates how much salt and water the kidneys retain in the body. Too much of this hormone results in .

Mutation in the CLCN2 gene alters blood pressure regulation

Familial hyperaldosteronism type II was first described in an Australian family 25 years ago. The research team investigated this family along with other patients suffering from hyperaldosteronism in childhood and adolescence. A total of eight families, including the large Australian family, showed mutations in a gene that had not previously been associated with . The CLCN2 gene carries information for building a channel in the cell membrane through which chloride ions can pass. In specific cells of the adrenal gland, these chloride channels regulate membrane voltage and aldosterone production. Gene mutations in patients with familial hyperaldosteronism cause changes in the membrane voltage and result in the overproduction of aldosterone, which raises .

Study results enable early detection and treatment

Lead author Ute Scholl says, "Patients with suspected familial hyperaldosteronism and their relatives will benefit from our findings because in the future, they can be screened for in the CLCN2 gene."

Study patients also responded to medication that is already used in the treatment of hyperaldosteronism. "For families with familial hyperaldosteronism type II, identifying the genetic cause doesn't just help with early detection of the disease, it also enables targeted treatment," says Scholl. As BIH Johanna Quandt Professor, Ute Scholl and her research group will now use the results from the study to delve deeper into their research at the Berlin Institute of Health. "We plan to further investigate the role of chloride channels in the adrenal gland," says Scholl. "We also try to better understand the regulation of these channels in order to develop improved treatment strategies."

Explore further: Research suggests new pathways for hyperaldosteronism

More information: Ute I. Scholl et al, CLCN2 chloride channel mutations in familial hyperaldosteronism type II, Nature Genetics (2018). DOI: 10.1038/s41588-018-0048-5

Related Stories

Research suggests new pathways for hyperaldosteronism

December 7, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP), in collaboration with researchers at Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the ...

Scientists discover a curable cause for some cases of high blood pressure

August 5, 2013
Five per cent of high blood pressure cases are caused by small nodules on hormone gland; now scientists have developed a scan which enables rapid diagnosis.

Simple blood tests lead to improved hypertension treatment in African countries

May 2, 2017
Using two simple blood tests, Western University researchers were able to drastically improve treatment for resistant hypertension across three sites in Nigeria, Kenya and South Africa.

Endocrine Society experts call for expanded screening for primary aldosteronism

April 26, 2016
The Endocrine Society today issued a Clinical Practice Guideline calling on physicians to ramp up screening for primary aldosteronism, a common cause of high blood pressure.

Researchers use a pump-induced disease to define underlying molecular mechanism

October 26, 2017
Researchers at Texas Tech University Health Sciences Center (TTUHSC) investigated a pump-induced disease and defined the molecular mechanism that triggers it. The study, "On the effect of hyperaldosteronism-inducing mutations ...

Diagnostic mutations ID'd in chronic kidney disease patients

December 5, 2017
(HealthDay)—About one-quarter of adults with chronic kidney disease (CKD) of unknown cause or familial nephropathy or hypertension have diagnostic mutations, which can be identified with whole-exome sequencing (WES), according ...

Recommended for you

New findings on autism-related disorder

May 24, 2018
In a study published today in Nature, Marc Bühler and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) have taken a major step forward in elucidating the mechanisms underlying a disorder known ...

Researchers discover cell structure that plays a role in epigenetic inheritance

May 22, 2018
We know a lot about how genes get passed from parent to child, but scientists are still unraveling how so-called epigenetic information—instructions about which genes to turn on and off—is conveyed from generation to ...

Fruit flies: 'Living test tubes' to rapidly screen potential disease-causing human gene

May 22, 2018
It all began with one young patient; a 7-year old boy who was born without a thymus, an important organ of the immune system, and without functional immune cells. The boy also presented with cardiac and skeletal defects, ...

Advance genetics study identifies virulent strain of tuberculosis

May 22, 2018
LSTM's Dr. Maxine Caws is co-lead investigator on an advanced genetics study published in Nature Genetics, which has shown that a virulent strain of tuberculosis (TB) has adapted to transmit among young adults in Ho Chi Minh ...

Cell types underlying schizophrenia identified

May 22, 2018
Scientists at Karolinska Institutet in Sweden and University of North Carolina have identified the cell types underlying schizophrenia in a new study published in Nature Genetics. The findings offer a roadmap for the development ...

New brain development disorder identified by scientists

May 22, 2018
Researchers have identified a new inherited neurodevelopmental disease that causes slow growth, seizures and learning difficulties in humans.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.