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Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

ABSTRACT: Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems.

SUBMITTER: Perrino PA

PROVIDER: S-EPMC7170883 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Perrino Peter A PA Talbot Lidiya L Kirkland Rose R Hill Amanda A Rendall Amanda R AR Mountford Hayley S HS Taylor Jenny J Buscarello Alexzandrea N AN Lahiri Nayana N Saggar Anand A Fitch R Holly RH Newbury Dianne F DF

Communications biology 20200420 1

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohort ...[more]

PMID: 32313182

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Project description:Hearing loss with increasing age adversely affects the ability to understand speech, an effect that results partly from reduced audibility. The aims of this study were to establish whether aging reduces speech intelligibility for listeners with normal audiograms, and, if so, to assess the relative contributions of auditory temporal and cognitive processing. Twenty-one older normal-hearing (ONH; 60-79 years) participants with bilateral audiometric thresholds ≤ 20 dB HL at 0.125-6 kHz were matched to nine young (YNH; 18-27 years) participants in terms of mean audiograms, years of education, and performance IQ. Measures included: (1) identification of consonants in quiet and in noise that was unmodulated or modulated at 5 or 80 Hz; (2) identification of sentences in quiet and in co-located or spatially separated two-talker babble; (3) detection of modulation of the temporal envelope (TE) at frequencies 5-180 Hz; (4) monaural and binaural sensitivity to temporal fine structure (TFS); (5) various cognitive tests. Speech identification was worse for ONH than YNH participants in all types of background. This deficit was not reflected in self-ratings of hearing ability. Modulation masking release (the improvement in speech identification obtained by amplitude modulating a noise background) and spatial masking release (the benefit obtained from spatially separating masker and target speech) were not affected by age. Sensitivity to TE and TFS was lower for ONH than YNH participants, and was correlated positively with speech-in-noise (SiN) identification. Many cognitive abilities were lower for ONH than YNH participants, and generally were correlated positively with SiN identification scores. The best predictors of the intelligibility of SiN were composite measures of cognition and TFS sensitivity. These results suggest that declines in speech perception in older persons are partly caused by cognitive and perceptual changes separate from age-related changes in audiometric sensitivity.

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Dataset Information

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Publications

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

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