Washington UniversityA genetic mutation discovered in four children born with multiple abnormalities could provide insight into probable treatments for infant lung distress and chronic obstructive pulmonary disease (COPD). Atleast this is what researchers from Washington University School of Medicine in St. Louis, McGill University, New York University Langone Medical Center claim.

The children were believed to have been born with abnormally developed lungs, gastrointestinal and urinary systems, skin, skull, bones and muscles. Additionally, all seemed to suffer from cutis laxa, which is a hereditary connective tissue disorder that causes the skin to hang loosely from the body. Three of the patients were noted to have died from respiratory failure before the age of two.

Elaine C. Davis, Ph.D., senior investigator and associate professor of anatomy and cell biology at McGill University in Montreal, Canada was believed to have compared various tissues from a mouse genetically engineered to be lacking a form of the LTBP4 gene with skin tissue samples from one of the children. This mouse is known to have been provided by Daniel Rifkin, M.D., the Charles Aden Poindexter Professor of Medicine and professor of cell biology at NYU Langone Medical Center.

She found amazing similarities, where the mouse showed identical connective tissue alterations via electron microscopy as compared to the child. She further found that the child seems to have cutis laxa, lethal pulmonary complications and gastrointestinal and urinary disease.

On the basis of these observations, researchers in the laboratory of Zsolt Urban were noted to have sequenced the LTBP4 gene in those four children and confirmed they had mutations.

Zsolt Urban Ph.D., assistant professor of pediatrics, of medicine and of genetics at Washington University School of Medicine recognized that the patients seem to be the foremost one to show severe symptoms of a novel syndrome. This new syndrome is noted to have been named as Urban-Rifkin-Davis Syndrome.

Chief investigator, Urban claimed that the findings seem to have probable implications for newborns with underdeveloped lungs and older patients with severe lung diseases, including COPD.

“Many newborns commonly have breathing difficulties. Part of the problem is that the lung is not developed properly, especially the alveoli, the tiny sacs at the end of the smallest airways that serve as a place for oxygen uptake and gas exchange. This finding helped us identify a gene essential for the development of alveoli and potentially provide a target for intervention in premature babies,” elucidates Urban.

Urban was of the opinion that potential treatments may perhaps include introducing the protein product of the LTBP4 gene to the newborn. Otherwise, making use of the existing drugs that could be able to moderate transforming growth factor beta (TGFß).TGFß appears to be overactivated in the tissues of these children.

Currently, the drug losartan is noted to be in trials for treating Marfan syndrome. This syndrome is known to be another connective tissue disorder. Losartan appears to have been shown to limit TGFß and claims added research as a possible treatment.

At present, the researchers seem to be expanding their research into the new syndrome among other patients with cutis laxa.

Urban further said that, “We are finding that about 70 percent of cutis laxa patients with pulmonary, gastrointestinal and urinary problems have Urban-Rifkin-Davis Syndrome. Now we will look at what percentage of cutis laxa patients with only pulmonary problems has the mutation.”

“Patients who may have a slightly reduced activity of LTBP4 might be more susceptible to chronic lung diseases later in life. Identifying genes that are central for the formation of alveoli may help us devise ways to regenerate alveoli in patients with COPD,” continues Urban.

He claimed that early developmental problems which are untraceable in childhood may influence a person to age-related disease such as COPD. Moreover, Urban along with his colleagues are believed to be analyzing samples collected from patients with COPD for LTBP4 mutations.

When lungs are damaged with COPD, alveoli appear to lose their elastic quality. Also, the walls between them may possibly get destroyed as they become thick and inflamed.

The findings of the research have been published in the online edition of the American Journal of Human Genetics.