Link be­tween autism and a can­cer gene

China Daily (Hong Kong) - - SCIENCE & TECHNOLOGY - By GINA KOLATA

Re­searchers study­ing two seem­ingly un­re­lated con­di­tions — autism and can­cer — have un­ex­pect­edly con­verged on a sur­pris­ing dis­cov­ery. Some peo­ple with autism have mu­tated can­cer or tu­mor genes that ap­par­ently caused their brain dis­or­der.

Ten per­cent of chil­dren with mu­ta­tions in a gene called PTEN, which cause can­cers of the breast, colon, thy­roid and other or­gans, have autism. So do about half of chil­dren with gene mu­ta­tions that can lead to some kinds of brain and kid­ney can­cer and large tu­mors in sev­eral or­gans. That is many times the rate of autism in the gen­eral pop­u­la­tion.

Dr. Evan Eich­ler, a pro­fes­sor of genome science at the Univer­sity of Wash­ing­ton, and oth­ers cau­tion that the find­ings ap­ply to only a small pro­por­tion of peo­ple with autism; in most cases, the cause re­mains a mys­tery. And not ev­ery­one with the mu­ta­tions de­vel­ops autism or can­cer, or other dis­or­ders as­so­ci­ated with the genes. But re­searchers say the find­ings are in­trigu­ing, given that they have no way of an­a­lyz­ing what might cause autism and no cure. The dis­cov­ery has en­abled sci­en­tists to ge­net­i­cally en­gi­neer mice with many symp­toms of the hu­man dis­or­der.

And it has led to the first clin­i­cal trial of a treat­ment for chil­dren with autism, us­ing the drug that treats tu­mors that share the same ge­netic ba­sis.

Richard Ewing of Nashville, Ten­nessee, a 10-year-old who has a form of autism caused by a tu­mor-caus­ing gene, is part of the new study. His par­ents, Alexan­dra and Rick Ewing, know he is at risk for tu­mors in the brain, heart, kid­ney, skin and eyes. But that bad news was tem­pered by his el­i­gi­bil­ity for the clin­i­cal trial, which just started. “There is a big dif­fer­ence be­tween us and the rest of the autism com­mu­nity,” Mr. Ewing said. “We have an hon­est-to-God ge­netic di­ag­no­sis.”

Not ev­ery­one agrees that the dis­cov­ery is so promis­ing. Steven McCar­roll, a ge­neti­cist at Har­vard Univer­sity, notes that autis­tic chil­dren with the can­cer gene mu­ta­tion have “a brain that is fail­ing in many ways.” Autism in th­ese chil­dren could be a man­i­fes­ta­tion of a gen­eral brain mal­func­tion, he said, adding, “The fact that autism is one of the many neu­ro­log­i­cal prob­lems that arise in th­ese pa­tients doesn’t nec­es­sar­ily tell us any­thing pen­e­trat­ing about the so­cial and lan­guage deficits that are spe­cific to autism.”

But other sci­en­tists say the work is chang­ing their un­der­stand­ing of autism. Like can­cer, autism can in­volve un­reg­u­lated growth of cells, in this case neu­rons in the brain.

Dr. Charis Eng, a can­cer ge­neti­cist at the Cleve­land Clinic in Ohio, first no­ticed a sur­pris­ing in­ci­dence of autism in chil­dren whose par­ents had the PTEN mu­ta­tion. In­ves­ti­ga­tors found that the rate of autism was about 10 times what would nor­mally be ex­pected.

At the same time, re­searchers found that an­other ge­netic dis­or­der was even more likely to re­sult in autism. That dis­or­der, tuber­ous Richard Ewing, 10, shown with

his fa­ther and sis­ter, is autis­tic and has a tu­mor­caus­ing ge­netic

mu­ta­tion. scle­ro­sis, in­creases the risk for kid­ney can­cer and a type of brain can­cer; half of tuber­ous scle­ro­sis pa­tients had autism.

The genes are part of a net­work of genes that puts a brake on cell growth. Dis­abling the genes re­leases that brake. One re­sult can be can­cer or tu­mors. An­other can be ab­nor­mal wiring of nerve fibers in the brain and autism.

Dr. Mustafa Sahin of Bos­ton Chil­dren’s Hos­pi­tal is test­ing whether drugs used to treat tu­mors caused by tuber­ous scle­ro­sis gene mu­ta­tions might treat autism in peo­ple with the mu­ta­tion.

He started with mice, delet­ing tuber­ous scle­ro­sis genes in their cere­bel­lums. Nerve fibers in the an­i­mals’ brains grew wildly, and the mice had un­usual be­hav­iors, rem­i­nis­cent of autism. But Ra­pamycin, which tar­gets the tuber­ous scle­ro­sis gene and blocks a pro­tein in­volved in cell di­vi­sion, changed the an­i­mals’ be­hav­ior.

Now Dr. Sahin is giv­ing a sim­i­lar drug, everolimus, to autis­tic chil­dren with a tuber­ous scle­ro­sis gene mu­ta­tion. Richard is part of that study.

Dr. Eich­ler fo­cused on autism that oc­curs with no fam­ily his­tory, re­cruit­ing 209 fam­i­lies with autis­tic chil­dren. He saw a strik­ing dif­fer­ence. Com­pared with their par­ents and sib­lings, the autis­tic chil­dren had two to three times as many mu­ta­tions that dis­abled a gene. Those genes were of­ten part of a path­way that con­trols cells growth. Re­searchers ini­tially thought the path­way’s link to autism was murky. “Then I said: ‘Wait, some of those genes are can­cer genes,’ ” Dr. Eich­ler said.

For An­drew and Lucy Dabi­nett’s son, Tommy, 9, whose autism is caused by a PTEN gene mu­ta­tion, there are no clin­i­cal tri­als yet.

Tommy has a limited vo­cab­u­lary, flaps his arms, rocks back and forth, and needs di­a­pers.

“I al­ready knew there was some­thing ter­ri­bly wrong with my child,” Ms. Dabi­nett said.

“Hon­estly,” she said, “it was a re­lief to have an an­swer.”


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