Genetic Cause of Two Common Male Reproductive Birth Defects Identified

The underlying genetic cause that triggers birth defects in newborn boys has been identified by a team of scientists.

Researchers at the Baylor College of Medicine, have successfully identified the genetic cause of two male reproductive birth defects namely cryptorchidism and hypospadias. Both defects can be surgically rectified during infancy.

During fetal development, when one or both the testes fail to descend into the scrotum, it is known as cryptorchidism. The second birth defect, namely hypospadias, is characterized by the abnormal placement of the opening of the urethra on the penis.

According to the study reports, about 3 percent of the full term male births suffer from cryptorchidism and the 1 in 125 births face hypospadias.

Led by Dr. Dolores Lamb, director of the Center for Reproductive Medicine at Baylor, the study used array comparative genomic hybridization, a genome wide screening method. This helps identify  alterations like duplication or deletions occurring in the chromosomal region, which are extremely minute to identify under a microscope. It is these genomic changes that can change the gene dosage and lead to a change in cell function.

During the analysis, the researchers noticed that it is a change in a number of gene copies called VAMP7 that causes these birth defects in children.

The study included 324 patients out of which gene duplication occurred in 1.35 percent of the patients.  But the gene duplication was not seen in 9,000 control subjects who did not have these birth defect.

 This association between gene duplication and the male reproductive tract birth defect was confirmed using a mouse model.  These mouse models mimicked the human genomic duplication and the same birth defects were observed in the mouse model as seen in human male infants

It was observed that the VAMP7 gene belonged to the SNARE protein family. "This SNARE protein traffics the movement of other proteins in the cell. No one had ever considered that a minor change in the amount of this protein could so profoundly impact the estrogen receptor and to a lesser extent androgen receptor action resulting in these male reproductive birth defects," researchers report.

The finding is documented in Nature Medicine.