An OTOF Frameshift Variant Associated with Auditory Neuropathy Spectrum Disorder

Area of Science:

• Genetics
• Neuroscience
• Ophthalmology

Background:

• Auditory Neuropathy Spectrum Disorder (ANSD) involves impaired auditory nerve activity with preserved outer hair cell function.
• Understanding the genetic underpinnings of ANSD is crucial for diagnosis and management.

Purpose of the Study:

• To identify the specific gene and genetic variant responsible for ANSD in a Chinese family.
• To investigate the molecular mechanism of the identified variant.

Main Methods:

• Whole exome sequencing was performed on a four-generation consanguineous Chinese ANSD family.
• Sanger sequencing was used to confirm variant co-segregation with the disease phenotype.
• Genetic analysis included 200 unrelated healthy individuals as controls.

Main Results:

• A homozygous c.1236delC variant in the otoferlin gene was detected in affected family members.
• This variant was absent in all 200 healthy controls.
• The c.1236delC variant is predicted to cause a truncated otoferlin protein, disrupting synaptic function.

Conclusions:

• The c.1236delC variant in the otoferlin gene is likely the causative mutation for ANSD in this family.
• This discovery enhances the understanding of otoferlin's role in auditory nerve function.
• Findings offer valuable information for genetic counseling of ANSD families.