ODD MUTATION TURNS BAD GENE GOOD

                         Roanoke Times
                 Copyright (c) 1995, Landmark Communications, Inc.

DATE: THURSDAY, February 18, 1993                   TAG: 9302180101
SECTION: NATIONAL/INTERNATIONAL                    PAGE: A-1   EDITION: METRO 
SOURCE: Associated Press
DATELINE: BOSTON                                LENGTH: Medium
ODD MUTATION TURNS BAD GENE GOOD
For the first time, scientists have found that a mutation can fix a bad human gene so it works normally again.
In these cases, the mutation corrected the genetic error that causes myotonic dystrophy, the most common adult form of muscular dystrophy. As a result, children who seemed destined to inherit the disorder avoided it.
"It's incredibly fascinating, and it's of great importance in terms of human genetics and disease," said Dr. Henry Epstein of Baylor College of Medicine.
Genes contain the code for the body to assemble proteins. Many inherited diseases arise when this code becomes garbled. As a result, the gene makes a defective protein or none at all.
In the case of myotonic dystrophy, mutations occur in a gene that contains instructions for making an enzyme that regulates proteins found in cell walls.
The disease affects about one in every 7,000 to 8,000 people worldwide. It causes weakness and wasting of muscles.
In today's issue of the New England Journal of Medicine, Dutch researchers report two cases in which children inherited their fathers' defective gene, but it had somehow become normal again, a process they call "reverse mutation."
The two people - a baby girl and a 25-year-old man - should have inherited muscular dystrophy, but did not. Instead, they "are examples of complete spontaneous corrections of myotonic dystrophy mutations," wrote Dr. Han G. Brunner and colleagues from University Hospital in Nijmegen.
Dr. Robert G. Korneluk and others from the University of Ottawa in Canada reported a similar case in the Feb. 5 issue of the journal Science. "It's brand-new genetics," Korneluk said. "That's what makes it fascinating."
The genetic defect involves the explosive copying of a fragment of genetic code. The more times this segment is repeated, the more severe the disease.
This piece of code, known in genetic shorthand as CTG, is repeated between five and 40 or so times in the gene of normal people. When defective, it contains anywhere from 50 to several thousand repeats. Typically the number of repeated sequences increases as the gene passes from parent to child.
People are born with two copies of the gene, one inherited from each parent. If one of the two genes is bad, then the child will get dystrophy.
In one of the Dutch cases, the child's gene contained 24 repeats of the CTG sequence, while the father's version contained up to 600. In the other case, the child's gene contained 19 while the father's had up to 500.
Such repairs probably are rare. Korneluk said he believes they happen in fewer than one in 1,000 myotonic dystrophy cases.
Precisely how, or even when, the gene gets fixed is a mystery. The change could have occurred during formation of the father's sperm, or it could have happened in the first stages of the embryo's development in the womb.
"I don't understand how it happens," said Korneluk, who studied an 18-year-old woman whose father had two copies of the gene but who shows no signs of myotonic dystrophy. "In the case of that individual, she just lucked out."

by Archana Subramaniam by CNB