Panel-based NGS reveals disease-causing mutations in hearing loss patients using BGISEQ-500 platform

Area of Science:

• Genetics
• Otolaryngology
• Molecular Diagnostics

Background:

• Hereditary hearing loss is genetically diverse, necessitating accurate mutation detection for diagnosis and family planning.
• Genetic testing is crucial for understanding the underlying causes of various hearing loss phenotypes.

Purpose of the Study:

• To develop and validate an effective method for detecting clinically relevant genetic alterations in hereditary hearing loss patients.
• To utilize target enrichment and next-generation sequencing for a comprehensive single-assay diagnosis.

Main Methods:

• Designed a custom array-based chip targeting 127 hearing loss-related genes.
• Performed targeted next-generation sequencing on 58 patients using the BGISEQ-500 platform.
• Analyzed sequencing data to identify disease-causing mutations.

Main Results:

• Successfully identified disease-causing mutations in 77.59% (45/58) of patients.
• Detected a total of 62 distinct mutations, including missense, Indel, splicing, synonymous, and copy number variants.
• Discovered 36 novel mutations (58.06%), significantly expanding the known mutation landscape for hearing loss.

Conclusions:

• The developed target enrichment and BGISEQ-500 sequencing method is highly effective for diagnosing hereditary hearing loss.
• This approach provides a powerful tool for precise molecular diagnostics in both syndromic and nonsyndromic hearing loss within the Chinese population.
• The findings enhance diagnostic capabilities and offer improved outcomes for patients and families affected by hearing loss.