Scientists have solved a century-old riddle _ and identified a genethat, when faulty, causes baldness _ in a rare inherited disease calledanhidrotic ectodermal dysplasia.
The disease was first reported more than a century ago by CharlesDarwin, who described a family in India in which 10 men all hadsparse hair, underdeveloped teeth, and "excessive dryness of theskin" despite India's steamy summers.
Now Anand Srivastava, of the J.C. Self Research Institute of HumanGenetics in Greenwood, S.C., and his colleagues report in the AugustNature Genetics that they have unraveled the genetic underpinningsof the disease, by identifying specific mutations and deletions thatcause the manifestations Darwin described.
Anhidrotic ectodermal dysplasia is one of 150 syndromescharacterized by abnormal development of the skin, hair, teeth andnails. All told, about 125,000 Americans are afflicted by thesesyndromes.
The name of the ailment _ which, loosely translated, meansabnormal development of the ectoderm compounded by an inabilityto sweat _ helps explain how a single gene can affect such seeminglydisparate bodily features as hair, teeth, nails and sweat glands.
As the name implies, the disease involves abnormal development ofthe ectoderm, which is embryonic skin. Ectoderm ultimately formsthe basis for the nervous system and sensory organs. It also developsinto hair, teeth, nails and sweat glands, typically within 12 weeks ofconception.
If the gene governing this transformation is faulty, the peculiar clusterof symptoms results. Most of those who suffer from it are men. "It isremarkable that no instance has occurred of a daughter being thusaffected," Darwin wrote.
This pattern of inheritance indicates that the gene responsible for thisdisorder resides on the X chromosome. Women have two copies ofthe chromosome, so their normal copy can take over for an abnormalone. But men have just one X chromosome and cannot compensate ifthe gene is flawed.
Srivastava and his colleagues began their search for the gene bydelving into the case of a woman who had the disorder. They wereaided by the fact that the woman had another genetic anomaly _ apiece of her X chromosome had broken off and attached itself toanother chromosome.
This enabled the team to fix on the translocated segment as a possiblesource of the genetic anomaly leading to anhidrotic ectodermaldysplasia.
Once they found the gene, they studied it in 15 other people who hadthe disorder. They found that all 15 had either mutations or deletionsin the gene.
Srivastava told BioWorld Today the team's next effort will be to findout how the gene functions. They plan to do this by studying themouse, which suffers from the rodent version of the rare humandisorder.
One way to go about this involves introducing a normal gene into themouse to determine whether that will repair the defect, Srivastavasaid. If the researchers can determine how the gene works, he said,they may be able to use the information to develop a means ofpreventing baldness.
In a separate study in the same journal, Christine Seidman, of theHoward Hughes Medical Institute at Harvard Medical School inBoston, and her colleagues reported they have identified a geneticflaw responsible for another unusual developmental failure in whichcertain teeth fail to form. They located the mutation by studying afamily in which 12 of 28 all men and women were missing preciselythe same two teeth, a molar and a premolar.
By analyzing the DNA of the affected family members, theresearchers found a mutation that accounts for the missing teeth. Thisflaw lies in a section of a gene that makes a protein geared to regulateother genes.
The anomaly lies in a region of the gene that is highly conserved in avariety of species and disrupts development of specific teeth,Seidman said.
Irma Thesleff, of the University of Helsinki, noted in anaccompanying commentary that it belongs to a family of genes thatplay an important role in orchestrating human development.
Although no one has yet determined the normal function of theanhidrotic ectodermal dysplasia gene, Thesleff said, its affects whenflawed indicate that the gene is also "part of some basicdevelopmental regulatory mechanism." n
-- Steve Sternberg Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.