Genetics and stem cells

Genetic link to stuttering

“Stuttering is less to do with nervousness and more to do with your genes,” reported The Daily Telegraph. The newspaper said researchers had identified three genes that were linked to the disorder, raising the possibility that new drug treatments could be developed.

Though these gene variants were more common in people who stuttered than a control group, only 5% of the stuttering group actually had these variants. This means that for 95% of the subjects, their stuttering was related to other genetic, environmental or social factors.

Further studies will be needed to test how common these genetic variants are in larger, more diverse populations. It is still unclear how stuttering is related to these genes. Greater understanding of this will be needed before this knowledge could possibly be used to develop a treatment for stuttering.

Where did the story come from?

This research was carried out by Dr Changsoo Kang and colleagues from a range of research institutes, including the National Institute on Deafness and Other Communication Disorders, the National Human Genome Research Institute and the Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

The study was supported by grants from the Intramural Research Program of the National Institute on Deafness and Other Communication Disorders, and the National Human Genome Research Institute in the US. The paper was published in the peer-reviewed peer-reviewed journal The New England Journal of Medicine .

Most newspapers have emphasised that this is early research.

What kind of research was this?

In this genetics study, the researchers analysed the genes of a large Pakistani family, of which many members from different generations had persistent stuttering. Several genetic variants, called single nucleotide changes (SNPs, which are single letter variations in the DNA sequence), were identified in 45 genes. The researchers focused on three of these genes, which they then extensively sequenced. This is a way of determining the order of the individual nucleotides, the building blocks of DNA.

The researchers explain that, as stuttering tends to run in families, they decided to look for the responsible genetic component in one such family. They already had an idea of where to look, as previous studies of families with stuttering suggested that the gene involved might lie on chromosome 12.

What did the research involve?

Genetic studies of stuttering are complicated by a high rate of spontaneous recovery and by the fact that non-genetic and social factors probably also have a role in the disorder. The researchers say that about 5% of children are thought to be affected by stuttering, but that most grow out of it, leaving about 1% of adults with persistent stuttering.

From the findings of a previous study of 46 Pakistani families affected by stuttering, the researchers identified an area of chromosome 12 to be of interest. They selected one of these families (referred to as PKST72) and extensively analysed the genetic sequence in the area of chromosome 12 for this family.

This analysis identified a number of genetic variations. The researchers then investigated whether these were more prevalent in family members that stuttered than those that did not, or than in the Pakistani population as a whole. A mutation within a gene called GNPTAB was found to be present in the DNA of most of the family members who stuttered (25 out of 28 individuals). Some members of the family who did not stutter carried copies of this variation, which lead the researchers to believe that some people who carry the mutation may not be affected.

The second part of the study involved looking for mutations in the GNPTAB gene in people who stuttered from a wider population sample from Pakistan and other countries. From their previous study in Pakistan, the researchers selected 46 unrelated people who stuttered and combined this with data from 77 other unrelated cases. These were compared to 96 people who did not stutter. They then recruited another 270 people who stuttered and 276 people who did not from Britain and the US.

The researchers then looked at the DNA sequence of the GNPTAB gene, as well as two related genes (GNPTG and NAGPA) in all the cases and controls to identify mutations that were associated with stuttering.

All three genes (GNPTAB, GNPTG, and NAGPA) carry instructions for making proteins involved in the transport of lysosomal enzymes. Lysosomes are small membrane-bound ‘sacs’ within cells that contain proteins (called enzymes) that break down large molecules into smaller molecules.

What were the basic results?

The researchers listed the mutations they found in the three genes GNPTAB, GNPTG, and NAGPA. They say that they found mutations in the three genes in 25 out of 786 chromosomes from unrelated stutterers compared with 4 of 744 chromosomes from the control subjects. This was a significant difference (P=0.0004).

How did the researchers interpret the results?

The researchers conclude that the tendency to stutter is associated with, “variations in genes governing lysosomal metabolism”.


This study indicates that in a selected group of affected people, persistent stuttering may be related to disturbances in lysosomal-related metabolic pathways. These findings warrant future research in this area.

A couple of points made by the authors and an accompanying editorial are noted:

  • The GNPTAB, GNPTG, and NAGPA variants were found in only a small proportion of cases, and together were present in 21 of the 393 unrelated, stuttering cases (about 5%). This highlights the fact that there are many other potential causes (in the other 95%) that still need investigation, some of which will be genetic and others may not.
  • Not all those with the genetic mutations identified in this study were affected by stuttering, also indicating that other factors could be affecting whether a person with the mutation stutters or not.
  • It is still not clear how the biological pathway, lysosomal transport, uncovered in this study acts to cause stuttering. The pathway acts in all cells and not just nerve cells responsible for speech.

Clearly more research in this area is needed and the researchers report that it is already under way. Only larger studies in community populations will show if this could then potentially lead to new drug treatments.

NHS Attribution