Stuttering, a speech problem that stigmatizes millions worldwide and has stumped scientists for centuries, could be caused by defects in three genes, a landmark study showed this week.
"People have speculated about the cause of stuttering for thousands of years and finally, we know at least some of the cause," Dennis Drayna, a geneticist and senior author of the study, which was published in the New England Journal of Medicine on Wednesday, told AFP.
Drayna was part of a team of scientists from the National Institute on Deafness and Other Communication Disorders (NIDCD) who analyzed the genes of 123 Pakistanis who stutter and 96 who do not, along with the genes of 550 people from the United States and England, around half of whom stuttered.
Some of the Pakistani study participants had been part of an earlier study that found that people who stutter -- a speech disorder in which a person repeats or prolongs sounds, syllables or words, disrupting the normal flow of speech -- had a mutation in a gene known as GNPTAB.
The new study found stutters had both the same GNPTAB mutations but also mutations in two other genes called GNPTG and NAGPA. People who did not stutter did not have the mutations.
The three genes play a role in steering enzymes to a cell structure called the lysosome where the enzymes break down and recycle cellular components.
Mutations in GNPTAB and GNPTG are already known to play a key role in two forms of mucolipidosis, a rare disorder where improperly recycled cell components accumulate in the lysosome and cause joint, skeletal, heart, liver, spleen and motor-system problems, along with developmental and speech problems.
NAGPA, which is also linked to the lysosome, was associated for the first time in this study with a disorder in humans -- stuttering.
The study is the first to "pinpoint specific gene mutations as the potential cause of stuttering, and by doing so, might lead to a dramatic expansion in our options for treatment," said James Battey, director of the NIDCD.
Drayna explained: "The mutations found in the study are in genes associated lysosomal disorders.
"A recent exciting development in lysosomal disorders is enzyme replacement therapy, where you simply give back the enzyme that is defective to people with the disorder," he told AFP.
"So we now have the exciting possibility that in future, we could also use enzyme replacement therapy to correct stuttering," he said.
The findings will also reassure parents of children who stammer, and help to remove the stigma associated with the speech problem, Jane Fraser, president of the Stuttering Foundation, told AFP.
"The findings of this study say this is biological. That will lift a burden of guilt from parents' shoulders," Fraser said.
"Everyday, we get hundreds of calls from parents and the first question mothers and fathers ask is: 'Did we cause our child's stuttering?' or 'What did we do wrong?' This will reassure them," Fraser said.
"And for adults who stutter, it will lift a stigma, because people won't be able to say things like 'It's all in his head' anymore," she said.
But, she added, therapists will have to continue to focus on the cognitive behavior therapies and speech tools they use now to help stutterers, as "any gene therapy for stuttering is a long way off."
Researchers at the University of Punjab in Lahore, Pakistan; the Hollins Communications Research Institute in Virginia, and other research institutes that, like NIDCD, are part of the US National Institutes of Health, also took part in the study.