Audiology and Speech Pathology - Research Publications

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Author: Bahlo, Melanie × Author: Reilly, Sheena × Author: Vogel, Adam × Type: Journal Article ×

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    Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40
    Morgan, AT ; Scerri, TS ; Vogel, AP ; Reid, CA ; Quach, M ; Jackson, VE ; McKenzie, C ; Burrows, EL ; Bennett, MF ; Turner, SJ ; Reilly, S ; Horton, SE ; Block, S ; Kefalianos, E ; Frigerio-Domingues, C ; Sainz, E ; Rigbye, KA ; Featherby, TJ ; Richards, KL ; Kueh, A ; Herold, MJ ; Corbett, MA ; Gecz, J ; Helbig, I ; Thompson-Lake, DGY ; Liegeois, FJ ; Morell, RJ ; Hung, A ; Drayna, D ; Scheffer, IE ; Wright, DK ; Bahlo, M ; Hildebrand, MS (OXFORD UNIV PRESS, 2023-12-01)
    Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.
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    Self-reported impact of developmental stuttering across the lifespan
    Boyce, JO ; Jackson, VE ; van Reyk, O ; Parker, R ; Vogel, AP ; Eising, E ; Horton, SE ; Gillespie, NA ; Scheffer, IE ; Amor, DJ ; Hildebrand, MS ; Fisher, SE ; Martin, NG ; Reilly, S ; Bahlo, M ; Morgan, AT (WILEY, 2022-10)
    AIM: To examine the phenomenology of stuttering across the lifespan in the largest prospective cohort to date. METHOD: Participants aged 7 years and older with a history of developmental stuttering were recruited. Self-reported phenotypic data were collected online including stuttering symptomatology, co-occurring phenotypes, genetic predisposition, factors associated with stuttering severity, and impact on anxiety, education, and employment. RESULTS: A total of 987 participants (852 adults: 590 males, 262 females, mean age 49 years [SD = 17 years 10 months; range = 18-93 years] and 135 children: 97 males, 38 females, mean age 11 years 4 months [SD = 3 years; range = 7-17 years]) were recruited. Stuttering onset occurred at age 3 to 6 years in 64.0%. Blocking (73.2%) was the most frequent phenotype; 75.9% had sought stuttering therapy and 15.5% identified as having recovered. Half (49.9%) reported a family history. There was a significant negative correlation with age for both stuttering frequency and severity in adults. Most were anxious due to stuttering (90.4%) and perceived stuttering as a barrier to education and employment outcomes (80.7%). INTERPRETATION: The frequent persistence of stuttering and the high proportion with a family history suggest that stuttering is a complex trait that does not often resolve, even with therapy. These data provide new insights into the phenotype and prognosis of stuttering, information that is critically needed to encourage the development of more effective speech therapies. WHAT THIS PAPER ADDS: Half of the study cohort had a family history of stuttering. While 75.9% of participants had sought stuttering therapy, only 15.5% identified as having recovered. There was a significant negative correlation between age and stuttering frequency and severity in adults.