Human Deletion Syndrome Research Articles

Trauma Centers Bleeding Dollars With Balance Sheets in the Red

In Texas, trauma centers lose, on average, $20 million each year. In California, losses total at least $400 million for the state’s major trauma centers, and the California Medical Association is calling for a $300 million infusion of cash into the state’s trauma system just to maintain the services. “Trauma care in Texas is imperiled,” claims Amir Rubin, chief operations officer at Hermann Hospital in Houston. “Texas’ trauma centers are currently delivering the highest levels of critical services to all Texans around the clock, regardless of HMO plan restrictions, regardless of insurance status. These trauma centers however, cannot sustain losses year after year and remain viable.” In Texas, where motorists rack up the highest number of annual motor vehicle accidents (3901 in 1999), trauma centers often mean the difference between life and death for accident victims, who make up the majority of their patients. However, according to a survey of the state’s Level I and II trauma centers by Mr Rubin, most centers are losing large amounts of money. Trauma in the uninsured population accounts for much of the increase during the past decade, according to Mr Rubin’s study. Twenty-one percent of Texans are without health insurance, he reported, with 31% of the population of Harris County (which includes Houston) and 25% of Dallas County uninsured. During the past year, the volume of trauma increased 5.4%, with concurrent increases in operating losses. At the same time, the federal government cut the funding that goes into state Disproportionate Share Payments. These payments were designed to help defray deficiencies between Medicaid payments and the cost of delivering Medicaid and indigent care (for which there is no reimbursement). Payments to private, nonprofit trauma centers declined 23% and those to public, district facilities dropped 11%. “The survey results reveal not only a bleak financial …

Deconstructing DiGeorge syndrome

DiGeorge syndrome is the most frequent contiguous-gene deletion syndrome in humans, occurring with an estimated frequency of 1 in 4,000 live births. Extensive microdeletion mapping in a large number of affected individuals has failed to identify a single gene or a combination of genes commonly deleted. Two new studies implicate the transcription factor TBX1 as a key candidate gene for the aortic arch malformations seen in DGS, and are consistent with the concept that some congenital diseases are caused by a reduced dosage of genes that control development. However, a similar study focusing on the adaptor protein Crkol shows that other genes within the deleted regions might affect the same developmental pathways.

Congenital heart disease in mice deficient for the DiGeorge syndrome region.

The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering.

Molecular approach to analyzing the human 5p deletion syndrome, cri du chat.

DNA unique or low-copy fragments were isolated from a genomic DNA library specific for the short (p) arm of human chromosome 5. These chromosome 5p-specific DNA fragments were used to analyze, by Southern blot experiments, somatic cell hybrids that retained either a normal chromosome 5 homolog or a homolog with a partial deletion of 5p, which was derived from either of two persons with the common human deletion syndrome, cri du chat or 5p- syndrome. In these studies, two classes of DNA fragments were identified, those located outside the region deleted in the persons with cri du chat and those located within the deleted region. This latter class of DNA probes will help to define, at the molecular level, a region of 5p that is critical in producing the phenotype associated with the cri du chat syndrome.