Navigation Links
Clue to genetic cause of fatal birth defect

A novel enzyme may play a major role in anencephaly, offering hope for a genetic test or even therapy for the rare fatal birth defect in which the brain fails to develop, according to a study from researchers at the University of Illinois at Chicago College of Medicine.

The study appears in the October issue of the journal of Molecular Endocrinology.

In the U.S., 1,000 to 2,000 children are born with anencephaly each year. Most do not survive more than a day or two. Although anencephaly can sometimes be diagnosed through ultrasound, which picks up the malformation of the head, there is no genetic test, and its cause is unknown.

By breeding special "knockout" mice that were missing the gene for the enzyme called HSD17b7, UIC researchers found that such mice died on the tenth day of gestation with the severe lack of brain development that characterizes the human birth defect.

The failure of the mice to develop, as well as the extreme nature of the changes in the formation of the animals, was very surprising, said Geula Gibori, UIC distinguished professor of physiology and biophysics and principal investigator of the study. Mice that lack enzymes of similar function are born with subtle changes in their cognitive ability, but they survive.

The UIC researchers had previously discovered this novel enzyme and were focused on its role in converting the weak hormone estrogen into the more potent estradiol in the ovaries and its possible role in breast cancer.

Recent research has shown that the HSD17b7 enzyme has an additional role in the last steps of cholesterol biosynthesis. But because the fetus receives cholesterol from the mother during gestation, Gibori and her colleagues did not expect the enzyme to be of much importance to development, she said.

However, it appears that as the fetal mouse brain develops it forms a blood barrier, blocking maternal cholesterol from brain cells. The brain becomes dependent on the biosynthesis of its own cholesterol once this blood-brain barrier forms, at day 10 of gestation.

The UIC researchers established that in the fetus, the brain is the most important site for HSD17b7 expression and provided evidence that anencephaly may result from the loss of this enzyme.

"Creating a knockout mouse is a very laborious process," said Aurora Shehu, first author of the paper and at that time a graduate student in Gibori's laboratory. Mice with only one copy of the gene are produced and then interbred; one in four of their offspring should have no copy of the gene -- a "null" mouse.

"We expected null mice to be born and to be infertile, however, no null mice were born," said Shehu. "I was afraid I had made a mistake, and went back to the beginning, repeating the entire process, but still no null mice were born."

Shehu then began more painstaking work, performing in-utero genetic testing on entire litters -- often 10 to 12 fetuses per litter. She found that the null mice were there, but they were dying at day 10 of gestation, when the blood-brain barrier develops.

Gibori says the gene that is missing or defective in human anencephaly is not yet known, but the discovery that the deletion of HSD17b7 in the mouse causes anencephaly suggests this gene may be awry in the human disease.

"This opens up very exciting possibilities for understanding human anencephaly, and, perhaps, someday being able to provide a genetic test for the condition early in pregnancy -- and ultimately a therapy," she said.

As their next step, Gibori's lab plans to test human anencephalic tissue for a mutation in the HSD17b7 gene.


Contact: Jeanne Galatzer-Levy
University of Illinois at Chicago

Related biology news :

1. American College of Medical Genetics receives $13.5M NIH contract
2. Genetic finding implicates innate immune system in major cause of blindness
3. Study finds genetic variant plays role in cleft lip
4. Genetic Engineering & Biotechnology News reports on growing role of molecular diagnostics
5. Rare genetic disorder gives clues to autism, epilepsy, mental retardation
6. Childrens Hospital researchers identify genetic mutation that may predict organ rejection
7. K-State professors USDA research shows mad cow disease also caused by genetic mutation
8. How do race, genetics and health-care disparities affect spread of HIV?
9. Exploding chromosomes fuel research about evolution of genetic storage
10. Genetics reveals big fish that almost got away
11. Scientists discover major genetic cause of colorectal cancer
Post Your Comments:
(Date:10/29/2015)... Oct. 29, 2015 Today, LifeBEAM ... partnership with 2XU, a global leader in technical ... smart hat with advanced bio-sensing technology. The hat ... to monitor key biometrics to improve overall training ... the two companies will bring together the most advanced ...
(Date:10/27/2015)... Calif. , Oct. 27, 2015 Synaptics Inc. ... solutions, today announced that Google has adopted the Synaptics ... touch controller solutions to power its newest flagship smartphones, ... by Huawei. --> ... like Google to provide strategic collaboration in the joint ...
(Date:10/26/2015)... 26, 2015  Delta ID Inc., a company focused ... and PC devices, announced its ActiveIRIS® technology powers the ... F-02H launched by NTT DOCOMO, INC in ... second smartphone to include iris recognition technology, after a ... F-04G in May 2015, world,s first smartphone to have ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... Orexigen® Therapeutics, Inc. (Nasdaq: OREX ) ... chat discussion at the Piper Jaffray 27th Annual Healthcare ... discussion is scheduled for Wednesday, December 2, at 8:00 ... replay will be available for 14 days after the ... NormartVP, Corporate Communications and Business Development , BrewLife(858) 875-8629 ...
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... , Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris Inc. ... IIROC on behalf of the Toronto Stock Exchange, confirms ... there are no corporate developments that would cause the ... --> --> About Aeterna Zentaris ... . --> Aeterna Zentaris is a specialty ...
(Date:11/24/2015)... LEXINGTON, Massachusetts , November 24, 2015 ... Officer, will participate in the Piper Jaffray 27 th Annual ... on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 p.m. ... Poulton , Chief Financial Officer, will participate in the Piper Jaffray ... City , NY on Tuesday, December 1, 2015, at 8:30 ...
Breaking Biology Technology: