Combined clinical, structural and cellular studies discriminate pathogenic and benign TRPV4 variants - Summary - MDSpire

Combined clinical, structural and cellular studies discriminate pathogenic and benign TRPV4 variants

  • By

  • Sarah H Berth

  • Linh Vo

  • Do Hoon Kwon

  • Tiffany Grider

  • Yasmine S Damayanti

  • Gage Kosmanopoulos

  • Andrew Fox

  • Alexander R Lau

  • Patrice Carr

  • Jack K Donohue

  • Maya Hoke

  • Simone Thomas

  • Chafic Karam

  • Alex J Fay

  • Ethan Meltzer

  • Thomas O Crawford

  • Rachelle Gaudet

  • Michael E Shy

  • Ute A Hellmich

  • Seok-Yong Lee

  • Charlotte J Sumner

  • Brett A McCray

  • July 18, 2024

  • 0 min

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Objective:

To evaluate the pathogenicity of TRPV4 variants using clinical data and experimental analyses, which is crucial for understanding their implications in patient care.

Key Findings:
  • Gain-of-function mutations in the TRPV4 ankyrin repeat domain affect RhoA interaction, which may have therapeutic implications.
  • Certain gain-of-function variants in the intrinsically disordered region may cause cytotoxicity, highlighting the need for targeted interventions.
  • Variants in the transmembrane domain are likely benign and do not cause gain of function, suggesting a pathway for genetic counseling.
  • Clinical features associated with pathogenic variants include congenital onset and motor-predominant disease, which can guide diagnosis.
Interpretation:

The study provides a framework for assessing TRPV4 variants, aiding in the identification of pathogenic mutations and informing patient selection for clinical trials, ultimately improving patient outcomes.

Limitations:
  • The study focuses on a limited number of variants and may not encompass all TRPV4 mutations, necessitating further research.
  • Clinical features may vary widely, complicating the assessment of pathogenicity, and highlighting the need for larger cohort studies.
Conclusion:

The findings enhance understanding of TRPV4 variant pathogenicity, which is crucial for future therapeutic strategies.

Original Source(s)

Combined clinical, structural and cellular studies discriminate pathogenic and benign TRPV4 variants

  • by Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A McCray

  • July 18, 2024

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