Prader-Willi syndrome

Prader lacks fader; Agelman misses mom?

At first glance, the two diseases have little in common. People with Prader-Willi syndrome display a lack of muscle tone, an odd facial structure, obesity and a low IQ. People with Angelman syndrome show severe retardation, puppet-like movements and uncontrollable bouts of laughter.

Yet new research suggests these diseases represent two sides of the same genetic coin. Moreover, geneticists examining the syndromes' molecular bases say Prader-Willi now appears to be the first concrete example in humans of a poorly understood genetic phenomenon called genetic imprinting, as well as the best evidence yet linking imprinting to human disease (SN: 5/20/89, p.312).

Most Prader-Willi cases occur when a particular segment of chromosome 15 gets deleted during embryonic development. Oddly, the syndrome results only when that deletion occurs in the chromosome 15 contributed by the father; the maternally contributed chromosome 15 in these patients is normal. But in about 40 percent of Prader-Willi cases, geneticists find no such deletion.

Robert D. Nicholls, Joan H.M. Knoll and Marc Lalande of the Children's Hospital in Boston and their co-workers performed genetic analyses on six families with Prader-Willi children who lack the characteristic chromosomal deletion. In all cases they found the patients had two maternal chromosome 15 segments and no paternal copy -- the result of a rare genetic error during early development. The syndrome provides "the first absolutely clear evidence in humans that it does make a difference which parent a gene comes from," comments geneticist Judith G. Hall of the University of British Columbia in Vancouver. Moreover, preliminary evidence suggests Angelman syndrome results when individuals inherit two paternal copies of the same segment on chromosome 15. The researchers reported their findings this week in Baltimore at the annual meeting of the American Society of Human Genetics and in the Nov. 16 NATURE.

Scientists have suspected that genetic imprinting -- a difference in gene expression dependent upon which parent contributed that gene -- might play a critical role in fetal and adult development, and may account for the unusual inheritance patterns of some diseases. Nicholls, now at the University of Florida College of Medicine in Gainesville, says the new findings should add to scientists' understanding of how genes regulate the exression of other genes -- knowledge that may someday aid in the diagnosis and treatment of genetic diseases.

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