PIEZO2 유전자의 유전된 돌연변이로 인한 감각 장애가 있는 건강한 지원자와 개인의 말초 신경에 대한 미세신경학적 평가

Study Description:

The study aims to characterize peripheral nerve function and physiology in healthy participants and participants with inherited mutations in the PIEZO2 gene (otherwise known as PIEZO2- Deficiency Syndrome [PDS]). PIEZO2 encodes a stretch-gated ion channel whose function has been shown to be essential for aspects of gentle touch sensation, vibration detection, mechanical allodynia and proprioception in humans. The physiological effects of PIEZO2 mutations on sensory neurons in humans are unknown. The study will improve our understanding of the molecular mechanisms for touch and mechanical pain sensation and determine if the peripheral neurons remain otherwise healthy in the absence of a functioning PIEZO2 channel.

Objectives:

Primary Objective:

To determine whether peripheral neurons have a blunted response to gentle mechanical stimulation (e.g., soft brushing) in PDS patients compared to healthy participants using direct electrical recording from peripheral nerves.

Secondary Objectives:

To examine the physiological properties of different types of mechanically sensitive sensory neurons in response to innocuous and noxious stimuli in PDS patients and healthy participants. We expect the loss of PIEZO2 to have greater impact on the responsiveness of certain types mechano-receptor subtypes over others.

Endpoints:

Primary Endpoint:

Our primary endpoint is evidence of reduced responsiveness (i.e., firing rate [Hz]) of peripheral neurons to gentle mechanical (brushing) stimulation in PDS patients compared to controls. We expect a reduction of at least 50% in firing rate (Hz).

Secondary Endpoints:

Our secondary endpoint is the emergence of a differential effect of the loss of PIEZO2 on mechanoreceptor subclasses. Mechanoreceptor subclasses will be identified using established criteria (e.g., stimulus sensitivity, receptive field size, spike morphology and axon conduction velocity). The effect of the loss of PIEZO2 on the responsiveness of single-unit subclasses will be quantified by firing rate measures on single-unit data. In addition, the percept evoked to intraneural electrical stimulation of single-unit subclasses will be noted.