Protein informatics combined with multiple data sources enriches the clinical characterization of novel TRPV4 variant causing an intermediate skeletal dysplasia

Stephanie L. Hines, John E. Richter, Ahmed N. Mohammad, Jain Mahim, Paldeep S. Atwal, Thomas Caulfield

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) is an ion channel permeable to Ca2+ that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. Pathogenesis of these phenotypes is not yet completely understood, but it is known that genotype–phenotype correlations for TRPV4 pathogenic variants often are not present. Methods: Newly characterized, suspected pathogenic variant in TRPV4 was analyzed using protein informatics and personalized protein-level molecular studies, genomic exome analysis, and clinical study. Results: This statement is demonstrated in the family of our proband, a 47-year-old female having the novel c.2401A>G (p.K801E) variant of TRPV4. We discuss the common symptoms between the proband, her father, and her daughter, and compare her phenotype to known TRPV4-associated skeletal dysplasias. Conclusions: Protein informatics and molecular modeling are used to confirm the pathogenicity of the unique TRPV4 variant found in this family. Multiple data were combined in a comprehensive manner to give complete overall perspective on the patient disease and prognosis.

Original languageEnglish (US)
Article numbere566
JournalMolecular Genetics and Genomic Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Informatics
Information Storage and Retrieval
Proteins
Exome
Transient Receptor Potential Channels
Phenotype
Sensory Receptor Cells
Osteoclasts
Chondrocytes
Nuclear Family
Ion Channels
Fathers
Virulence
Genes

Keywords

  • Kozlowski type
  • Maroteaux type
  • skeletal dysplasia
  • spondyloepiphyseal dysplasia
  • spondylometaphyseal dysplasia
  • transient receptor potential cation channel subfamily V member 4 (TRPV4)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Protein informatics combined with multiple data sources enriches the clinical characterization of novel TRPV4 variant causing an intermediate skeletal dysplasia. / Hines, Stephanie L.; Richter, John E.; Mohammad, Ahmed N.; Mahim, Jain; Atwal, Paldeep S.; Caulfield, Thomas.

In: Molecular Genetics and Genomic Medicine, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) is an ion channel permeable to Ca2+ that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. Pathogenesis of these phenotypes is not yet completely understood, but it is known that genotype–phenotype correlations for TRPV4 pathogenic variants often are not present. Methods: Newly characterized, suspected pathogenic variant in TRPV4 was analyzed using protein informatics and personalized protein-level molecular studies, genomic exome analysis, and clinical study. Results: This statement is demonstrated in the family of our proband, a 47-year-old female having the novel c.2401A>G (p.K801E) variant of TRPV4. We discuss the common symptoms between the proband, her father, and her daughter, and compare her phenotype to known TRPV4-associated skeletal dysplasias. Conclusions: Protein informatics and molecular modeling are used to confirm the pathogenicity of the unique TRPV4 variant found in this family. Multiple data were combined in a comprehensive manner to give complete overall perspective on the patient disease and prognosis.",
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AU - Atwal, Paldeep S.

AU - Caulfield, Thomas

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