Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

40-Hz Auditory Steady State Response (ASSR) as a Biomarker of Abnormalities in SHANK3 Gene: a Case-Report of 15-years Old Girl with Rare Microduplication in 22q13.33

Version 1 : Received: 27 November 2020 / Approved: 30 November 2020 / Online: 30 November 2020 (08:33:26 CET)

A peer-reviewed article of this Preprint also exists.

Journal reference: International Journal of Molecular Sciences 2021
DOI: 10.3390/ijms22041898


SHANK3 encodes scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+inhibitory neurons – the key players in generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response(ASSR). Here we describe a clinical and neurophysiological phenotype of a 15-years old girl (SH01) with microduplication of 16389 bp in 22q13.33, affecting the SHANK3 gene in comparison to typically developing children (n=32). EEG were recorded during the binaurally presentation of 40-Hz clicks’ trains lasting for 500 ms with inter-trial intervals 500-800 ms. SH01 was diagnosed with mild mental retardation and learning disabilities(F70.88) and had problems with reading and writing, as well as smaller vocabulary than TD peers. Her clinical phenotype generally resembled the phenotype of previously described patients with 22q13.33 microduplication. SH01 had mild autistic symptoms but below the threshold for ASD diagnosis. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential(ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. Absence of 40-Hz ASSR in patient with microduplication, affected SHANK3 gene, indicates deficient temporal resolution of the auditory system, that might underlie language problems, and represent neurophysiological biomarker of SHANK3 abnormalities.


22q13.3 duplication; Auditory steady state response, ASSR; SHANK3; biomarker; auditory event-related potential, ERP; autism spectrum disorders; intellectual disabilities



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