Using mouse models, researchers from King’s College London provide a clue as to why patients with CHARGE syndrome are deaf. Recently published in the journal Communications Biology, their findings suggest that a faulty stress response leads to the death of cells involved in sound perception.
CHARGE syndrome is a complex genetic disorder with a known pattern of features. It affects the development and function of different organs, including the ear, eye, heart, and genitals.
The major causes of CHARGE syndrome are mutations in a gene called CHD7. Most CHARGE patients suffer from hearing loss, but the reasons for this are still unclear.
“In the ear, sound is perceived by specialized cells – the so-called hair cells – and transmitted to the brain by the neurons that innervate them,” explains lead author of the study, Dr. Mohi Ahmed from the Centre for Craniofacial & Regenerative Biology at King’s College London. “Because of their high oxygen demand, these cells are particularly sensitive to stress.”
Using mouse models of CHARGE syndrome, Ahmed and colleagues examined the development of hair cells and neurons in the ear. To their surprise their development was normal. Instead, hair cells and neurons degenerated after birth, ultimately leading to hearing loss. On a molecular level, CHD7 controls the machinery that determines how cells respond to stress. The authors show that when CHD7 is mutated, hair cells are hypersensitive to stress. This observation provides an explanation for deafness in CHARGE patients suggesting that hair cells die rapidly upon sound exposure.
Co-author, Andrea Streit, Professor of Developmental Neurobiology at King’s said: “Our findings suggest that developing new treatments to prevent hair cell death shortly after birth may help to prevent hearing loss in CHARGE syndrome. Continued research is needed to help us understand the medical and developmental challenges facing individuals with CHARGE.”
“Our findings also raise the interesting possibility that some neurodegenerative diseases arise from the developmental abnormalities that go undetected, and that hearing loss may be an early indicator for these conditions.”