FHL-1 Mutation Screening for X-linked Muscular Myopathy Diagnosis
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Solution Overview
Problem
There is a need to identify and screen for Four and a Half LIM domains protein 1 (FHL-1) mutations associated with muscular myopathies, including muscular dystrophy and cardiomyopathy, to diagnose and predict the risk of developing these conditions.
Innovation Solution
A protein comprising amino acids 1-230 or a fragment thereof with a specific amino acid sequence, along with its encoding nucleic acid, is used for screening, including a method to assay biological samples for mutations such as an isoleucine insertion at position 128 in the FHL-1 protein, employing PCR, probe hybridization, or sequencing, and a kit containing antibodies and reagents for diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to screen for muscular dystrophy mutations, then Duchenne and Becker muscular dystrophy can be detected, but novel X-linked muscular myopathies caused by FHL-1 mutations cannot be identified
Solution Approach 1:
The patent develops a screening method that can detect multiple types of muscular dystrophy mutations simultaneously. The assay is designed to screen for both conventional DMD gene mutations and novel FHL-1 gene mutations associated with X-linked muscular myopathies, making the diagnostic tool universal across different muscular dystrophy types rather than limited to specific conditions
Solution Approach 2:
The patent identifies and targets specific mutation types in the FHL-1 gene, including frameshift mutations, missense mutations, and inframe deletions. By segmenting the screening approach to detect these specific mutation categories, the method achieves comprehensive coverage of FHL-1 related myopathies while maintaining the ability to detect conventional DMD mutations
2Adaptability or versatility
If FHL-1 mutation screening is added to existing protocols, then novel X-linked muscular myopathies can be identified, but the complexity of the screening process increases
Solution Approach 1:
The patent combines FHL-1 mutation screening with existing DMD gene screening protocols into a single integrated assay. By merging the detection of both gene types into one comprehensive screening process, the method expands coverage to include novel X-linked muscular myopathies without requiring separate, additional testing steps
Solution Approach 2:
The screening method is designed as a universal platform that handles multiple gene targets (DMD and FHL-1) and multiple mutation types (frameshift, missense, inframe deletions) through a single protocol, reducing the operational complexity that would otherwise arise from implementing separate screening procedures
3Reliability
If comprehensive mutation screening is performed, then all types of muscular dystrophy can be diagnosed, but the cost and time required for screening increases
Solution Approach 1:
The patent employs a preliminary screening approach that first identifies potential FHL-1 mutations using targeted assays designed to detect specific mutation types (frameshift, missense, inframe deletions). This preliminary action allows for efficient identification of high-probability cases before proceeding to more comprehensive analysis, reducing overall screening time while maintaining diagnostic accuracy
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables effective identification and risk prediction of X-linked muscular myopathies by specifically targeting FHL-1 mutations, providing a diagnostic tool for muscular dystrophy and cardiomyopathy.
Implementation Method 1
c) that is capable of hybridizing to a nucleic acid encoding the protein as defined above or fragment thereof under stringent hybridization conditions
Implementation Method 2
assaying the sample for a nucleic acid encoding the protein as defined above or a fragment thereof comprising the amino acid sequence VAKKCX1GX2X3NPIT
Data Source
AI summary
Four and a Half LIM domains protein 1 (FHL-1) mutations at positions 128 or 224 that are associated with X-linked muscular myopathy, methods of screening subjects to identify those susceptible to muscular myopathy including muscular dystrophy and cardiomyopathy and kits.