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The pathophysiology underlying spiral ganglion cell defect–induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron–like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron–like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron–like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss., Dysfunctions of spiral ganglion neurons caused by Map1b deficiency leads to sensorineural hearing loss.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a chronic disorder characterized by repetitive apneas, oxygen desaturation and disruption during sleep. The main clinical manifestations of OSAHS are snores, intermittent hypoxia, morning headache, excessive daytime sleepiness, tired and memory descent. OSAHS affects 3%-20% of the general population. Although commonly accepted as the gold standard for diagnosis of OSAHS, PSG is thought to be time-consuming, labor-intensive, costly and uncomfortable. Evidence from epidemiology indicated that 93% of women and 82% of men with moderate to severe OSAHS have not been clinically diagnosed. An epidemiological survey in Shanghai, China, showed that more than 85% of OSAHS was undiagnosed. Studies showed that undiagnosed OSAHS is independently associated with the increased likelihood of hypertension, cardiovascular diseases, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Thus, researchers have attempted to develop a simple and effective tool to screen patients with OSAHS, which has been reviewed and summarized in our article.