NGS Multigene Panel for Hereditary Hearing Loss Diagnosis
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Solution Overview
Problem
Current genetic testing methods for hereditary hearing loss-related disorders like Usher syndrome, Pendred syndrome, and Lange-Nielsen syndrome are invasive, time-consuming, and have limited mutation coverage, making it difficult to rapidly and accurately diagnose infants at risk, especially since they require cumbersome sample preparation and specialized equipment.
Innovation Solution
A next-generation sequencing (NGS) based multigene panel testing method that detects mutations in a panel of 24 hereditary hearing loss-related genes, including ABHD12, ADGRV1, CDH23, and others, using a biosampling device and lysis buffer, allowing for rapid and non-invasive detection of mutations in biological samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If next-generation sequencing (NGS) is used to detect multiple gene alterations in a single assay, then the coverage of mutations detected is improved, but the complexity of sample preparation and equipment requirements increases
Solution Approach 1:
The patent extracts and isolates specific target genes related to hereditary hearing loss from the complex genomic DNA, using hybridization capture technology to selectively enrich only the relevant sequences. This allows NGS to focus on a manageable set of target genes while maintaining high mutation coverage, effectively reducing the complexity burden of analyzing the entire genome.
Solution Approach 2:
The patent introduces hybridization capture probes as an intermediary between the genomic DNA and the sequencing process. These probes selectively bind to target gene sequences, serving as a mediator that simplifies the sample preparation by pre-enriching the DNA library with only the relevant sequences before sequencing, thus reducing equipment and procedural complexity.
2Ease of operation
If traditional genetic testing procedures are used, then sample preparation is straightforward, but the time required for diagnosis and length of stay in neonatal intensive care unit increases
Solution Approach 1:
The patent performs preliminary enrichment of target DNA sequences using hybridization capture before sequencing. This preliminary action concentrates the relevant genetic material in advance, allowing the actual sequencing and diagnosis to proceed faster. The pre-enrichment step simplifies subsequent processing and reduces the overall diagnosis time while maintaining ease of operation.
Solution Approach 2:
The patent changes the parameters of the sequencing assay by using targeted hybridization capture followed by high-throughput sequencing, rather than traditional Sanger sequencing. This parameter change enables parallel processing of multiple genes, dramatically reducing diagnosis time while the standardized protocol maintains operational simplicity.
3Device complexity
If a narrow range of mutations is tested for a limited number of hearing loss-related disorders, then the testing procedure is simpler, but the ability to diagnose diverse hereditary hearing loss disorders is reduced
Solution Approach 1:
The patent creates a universal testing platform that can detect mutations across multiple genes associated with different hereditary hearing loss disorders (Usher syndrome, Pendred syndrome, Jervell syndrome, Lange-Nielsen syndrome). The hybridization capture probes are designed to target multiple genes simultaneously, allowing a single assay to serve multiple diagnostic functions and increasing versatility without proportionally increasing complexity.
Solution Approach 2:
The patent merges the detection of multiple hearing loss disorders into a single integrated NGS assay. By combining target enrichment for multiple genes into one hybridization capture step and sequencing them together, the patent achieves broad disorder coverage while maintaining a streamlined testing procedure that is more efficient than multiple separate tests.
4Quantity of substance
If large blood volume is collected for genetic testing, then sufficient nucleic acid for analysis is obtained, but the safety and ease of sampling from infants is reduced
Solution Approach 1:
The patent changes the parameter of nucleic acid extraction efficiency by using optimized hybridization capture conditions and highly efficient DNA extraction methods. This allows sufficient nucleic acid quantity to be obtained from smaller blood volumes, reducing the sampling burden and risk to infants while maintaining adequate material for comprehensive multi-gene sequencing analysis.
Data Source
AI summary
The present disclosure provides kits, methods, and assays for detecting one or more mutations associated with hereditary or syndromic hearing loss. The method can comprise performing a multigene panel sequencing assay on a biological sample extracted from a subject to identify one or more mutations associated with hearing loss. The disclosed kits, methods, and assays may be particularly useful for determining whether an infant patient is a carrier for or is at risk for developing a hereditary hearing loss-related disorder such as Usher syndrome, Pendred syndrome, Jervell syndrome, and Lange-Nielsen syndrome.