ZFYVE26 Gene Mutation Detection for Hereditary Spastic Paraplegia Diagnosis

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Solution Overview

Problem

Current diagnostic methods for hereditary spastic paraplegias (HSP) lack effective tools for identifying mutations in the ZFYVE26 gene, which are associated with Autosomal Recessive Hereditary Spastic Paraplegia (AR-HSP), leading to delayed or inaccurate diagnosis and inadequate genetic counseling.

Innovation Solution

The identification of mutations in the ZFYVE26 gene, including specific substitutions, deletions, insertions, and complex rearrangements, using ex vivo methods, isolated nucleic acids, and monoclonal or polyclonal antibodies to detect truncated forms of the spastizin protein, enabling precise diagnosis and genetic counseling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods are used for HSP, then diagnosis can be performed with existing tools, but identification of ZFYVE26 gene mutations is not possible leading to delayed or inaccurate diagnosis

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidmutation detection capability
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The diagnostic approach is segmented into multiple specific detection methods targeting different types of ZFYVE26 mutations (substitutions, deletions, insertions, complex rearrangements). Each detection method is optimized for specific mutation types, enabling comprehensive and accurate identification that was not possible with previous general diagnostic tools.

Inventive Principle:
Principle #1Segmentation

2Reliability

If ex vivo methods and specific antibodies are used to detect truncated spastizin protein forms, then precise diagnosis is enabled, but diagnostic complexity and required resources increase

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoiddiagnostic method complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Monoclonal and polyclonal antibodies serve as intermediaries that specifically recognize and bind to truncated forms of the spastizin protein. These antibodies enable detection of mutation-induced protein changes without requiring direct genetic analysis, thereby improving diagnostic reliability while using well-established immunological techniques.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If comprehensive mutation screening is performed in ZFYVE26 gene, then accurate genetic counseling is possible, but time and resource requirements increase

Engineering Contradiction:
Improvegenetic information completenessVSAvoiddiagnosis time
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The patent establishes a comprehensive mutation spectrum and diagnostic protocol in advance, identifying all relevant mutation types (substitutions, deletions, insertions, complex rearrangements) and their locations in the ZFYVE26 gene. This preliminary characterization enables rapid and accurate screening without requiring de novo analysis for each patient, reducing diagnostic time while maintaining completeness.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP2268837B1Diagnosis of hereditary spastic paraplegias (HSP) by identification of a mutation in the zfyve26 gene or protein
Publication Date: 2018.02.07 UNIVERSITE DE BORDEAUX
  • EP2268837B1 patent drawingFigure 1
  • EP2268837B1 patent drawingFigure 1
  • EP2268837B1 patent drawingFigure 2A~2C

AI summary

The Invention relates to an ex vivo method of diagnosing or predicting a hereditary spastic paraplegias (HSP), in a subject, which method comprises detecting a mutation in the ZFYVE26 gene or protein (spastizin), wherein said mutation is indicative of a hereditary spastic paraplegias (HSP).