New Complexities in the Genetics of Stuttering: Significant Sex-Specific Linkage Signals

Abstract

Stuttering is a speech disorder long recognized to have a genetic component. Recent linkage studies mapped a susceptibility locus for stuttering to chromosome 12 in 46 highly inbred families ascertained in Pakistan. We report here on linkage studies in 100 families of European descent ascertained in the United States, Sweden, and Israel. These families included 252 individuals exhibiting persistent stuttering, 45 individuals classified as recovered from stuttering, and 19 individuals too young to classify. Primary analyses identified moderate evidence for linkage of the broader diagnosis of "ever stuttered" (including both persistent and recovered stuttering) on chromosome 9 (LOD = 2.3 at 60 cM) and of the narrower diagnosis of persistent stuttering on chromosome 15 (LOD = 1.95 at 23 cM). In contrast, sex-specific evidence for linkage on chromosome 7 at 153 cM in the male-only data subset (LOD = 2.99) and on chromosome 21 at 34 cM in the female-only data subset (LOD = 4.5) met genomewide criteria for significance. Secondary analyses revealed a significant increase in the evidence for linkage on chromosome 12, conditional on the evidence for linkage at chromosome 7, with the location of the increased signal congruent with the previously reported signal in families ascertained in Pakistan. In addition, a region on chromosome 2 (193 cM) showed a significant increase in the evidence for linkage conditional on either chromosome 9 (positive) or chromosome 7 (negative); this chromosome 2 region has been implicated elsewhere in studies on autism, with increased evidence for linkage observed when the sample is restricted to those with delayed onset of phrase speech. Our results support the hypothesis that the genetic component to stuttering has significant sex effects.

Eletromiografia e diadococinesia: estudo com crianças fluentes e com gagueira

“…[8][9][10][11][12][13] Although the subjacent nucleus of PDS still remains unclear, there is a strong body of evidence suggesting that PDS is a hereditary disorder which manifestation is a dysfunction in central motor speech control. [14][15][16][17][18][19][20] In Freed's21 model, the neuromuscular processing can be investigated through evidence given by the behavior of muscles that contribute to normal speech production. If any of these traces are in some way compromised, the motor system will be negatively affected.…”

Recent advances in genetic studies of stuttering

“…Half of the stutterers had a family history, and risk to first degree relative was 15%. Several large families with multiple individuals were affected by stuttering [10][11][12][13][14][15].…”

“…These puzzling clinical features, and the fact that stuttering has its origin in the brain, hinder researchers from investigating the neural basis of stuttering. However, several genetic studies such as twin, adoption, and segregation studies have suggested that this disorder occurs by the inheritance of gene mutations [9][10][11][12][13][14][15][16]. Genetic evidence presented by several approaches, in particular, genome-wide linkage analysis have shed light on these causative genes.…”

Diadococinesia sequencial em crianças fluentes e com gagueira desenvolvimental persistente: análise da velocidade e tipo do erro da consoante alvo

“…The likely source of stuttering that is genetically transmitted is the inability to automatically update internal models (related to the dynamics of the execution motor control effector system), leading to the sensorial consequences of movement repetition or blockage, preventing the completion of the motor order issued, and causing a continuous reinitialization of the system. Stuttering symptomatology (involuntary disruptions of speech flow) changes speech naturalness, making communication stressful, challenging, and frustrating (13,14,15,16,17,18) . One of the tests used to assess speech motor production is diadochokinesis (DDK), used to determine the speed and regularity of the movements of the jaw, lips, and tongue.…”