CFTR Mutation Screening Panel for Cystic Fibrosis Diagnosis
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Solution Overview
Problem
Current genetic screening methods for cystic fibrosis (CF) are inadequate for accurately diagnosing CF and related disorders, particularly in non-Caucasian populations, as they fail to detect a comprehensive set of CFTR mutant alleles beyond the AF508 mutation.
Innovation Solution
The development of methods and systems for testing CFTR gene mutations, including nucleic acid sequencing, hybridization, and protein analysis, using novel mutations identified in the CFTR gene to diagnose CF and related disorders, which can be used in combination with existing methods for more accurate genetic testing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current genetic screening methods focus only on the AF508 mutation, then the screening process is simple and cost-effective, but the diagnostic accuracy is insufficient for non-Caucasian populations and patients with atypical CF
Solution Approach 1:
The patent segments the CFTR gene into multiple specific mutation sites (13 mutations across different exons) that can be tested individually or in combinations. This segmentation allows the screening method to cover diverse genetic variations without requiring analysis of the entire gene, thereby improving diagnostic accuracy while maintaining manageable complexity.
Solution Approach 2:
The patent develops a universal screening panel that detects multiple CFTR mutations (including but not limited to AF508) using a single comprehensive test design. This multi-functional approach enables the same screening method to serve diverse patient populations (Caucasian, African American, Hispanic, Asian) and different clinical scenarios (classical CF, atypical CF, carrier screening), resolving the contradiction between accuracy and complexity.
2Reliability
If comprehensive CFTR mutation screening is performed to improve diagnostic accuracy, then more mutations can be detected, but the cost and complexity of testing increase
Solution Approach 1:
The patent performs preliminary identification and characterization of specific high-impact CFTR mutations (13 key mutations) before developing the screening panel. This preliminary action allows the creation of a focused, pre-validated test that reliably detects the most clinically significant mutations without requiring laboratories to develop and validate an exhaustive panel of all possible CFTR variants, thus improving reliability while maintaining ease of implementation.
3Productivity
If only the most common AF508 mutation is screened, then the testing process is straightforward, but patients with rare or population-specific mutations receive false negative results
Solution Approach 1:
The patent changes the parameter of mutation coverage from single-mutation (AF508 only) to multi-mutation panel (13 mutations including rare and population-specific variants). This parameter change expands detection capability across different ethnic groups and disease presentations while maintaining screening efficiency through a standardized panel format that can be implemented using high-throughput methodologies.
Data Source
AI summary
The present invention provides novel mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that can be used for a more accurate diagnosis of cystic fibrosis (CF) and CF related disorders. Methods for testing a sample obtained from a subject to determine the presence of one or more mutations in the CFTR gene are provided wherein the presence of one or more mutations indicates that the subject has CF or a CF related disorder, or is a carrier of a CFTR mutation.