Anhidrotic Ectodermal Dysplasia Disorder
In 1875, Charles Darwin found a new disorder that appeared in each generation of a family, affecting some of the male members and not others. This condition was more prominent in very young people. Darwin also found that the daughters were never affected although they could transmit the disease to their sons, although no males have ever transmitted the disease to their sons. Darwin started the research that led to the discovery of the gene for anhidrotic ectodermal dysplasia (EDA).10
In the early 1970's, the EDA gene became one of the first gene linked to the X chromosome. An international team of scientists, led by Dr. Juha Kere of the University of Helsinki and Dr. Anand Srivastave from the University of Washington in St. Louis identified the location and the structure of the gene that causes the EDA disorder. The National Institute of Health, the National Institute of Dental Research, and the National Center for Human Genome Research helped sponsor this work at the National Institutes of Health. Scientists provided a molecular marker to identify female carriers of the disorder, and are a step closer to developing the therapeutic interventions to prevent or alleviate symptoms in affected individuals.2
Still, very little is known about what occurs at the molecular level to produce the features of EDA. "Dysplasia" refers to the abnormal development of the tissues, skin, hair, sweat glands, nails, and teeth. The term "anhidrotic" refers to the underdevelopment or absence of sweat glands. This could be life threatening due to the fact that it prevents the body from cooling itself down during things like fevers or hot days.
Of more than 150 different types of ectodermal dysplasia, mutations in the X chromosome account for about half of the cases. The "X linked" form of ectodermal dysplasia is associated with male children. Males have only a single X chromosome inherited from the mother, along with a Y chromosome from the father. So, males don't have another X chromosome to cover up the infected genes. Women on the other hand, have two X chromosomes and are more likely to not show any symptoms of the abnormal gene.
Two female patients with all the symptoms of X-linked EDA led Dr. Kere, Dr. Srivastave, and other colleagues to the discovery of this gene. Earlier work by Jonathan Zonana, identified an unusual chromosomal rearrangement in one of the girls. The X chromosome had been sheared in two, with one piece sticking to the end of chromosome 9 and the remainder forming a truncated X. A similar X translocation was identified by other investigators in the second girl. Although the break points occurred in slightly different locations, both destroyed the function of the EDA gene. This indicated that the breaks occurred within the region of the chromosome that contains the gene. In other disorders where X translocations have been identified as the cause, the normal X chromosome is...