Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Genetic defect responsible for the dysfunctional protein: factor IXLong Beach.

J Ware1, L Davis, D Frazier

  • 1Department of Biology, University of North Carolina, Chapel Hill 27599-3280.

Blood
|August 1, 1988
PubMed
Summary

A genetic mutation in the factor IX Long Beach (FIXLB) gene causes hemophilia-B by altering a key amino acid. This FIXLB variant shows impaired function, highlighting a critical residue in factor IX activity.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC.

Journal of neonatal-perinatal medicine·2023
Same author

Correlation of placental pathology with the postoperative outcomes and white matter injury in preterm infants following necrotizing enterocolitis.

Journal of neonatal-perinatal medicine·2023
Same author

Nutrition management guideline for propionic acidemia: An evidence- and consensus-based approach.

Molecular genetics and metabolism·2019
Same author

Functional Study of the Vitamin K Cycle Enzymes in Live Cells.

Methods in enzymology·2017
Same author

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

Journal of thrombosis and haemostasis : JTH·2015
Same author

Structural and functional insights into enzymes of the vitamin K cycle.

Journal of thrombosis and haemostasis : JTH·2015

Area of Science:

  • Molecular Biology
  • Hematology
  • Genetics

Background:

  • Hemophilia-B is a bleeding disorder caused by deficiency in functional factor IX (FIX).
  • The factor IX Long Beach (FIXLB) variant presents with hemophilia-B, but its precise molecular defect was not fully characterized.

Purpose of the Study:

  • To identify the specific genetic mutation responsible for the FIXLB variant.
  • To elucidate the molecular mechanism underlying the impaired function of FIXLB.

Main Methods:

  • DNA sequencing of the FIXLB gene, including exons and flanking introns.
  • Isolation and characterization of genomic DNA clones.
  • Amino acid sequence prediction and analysis.

Main Results:

Related Experiment Videos

  • A thymine to cytosine transition mutation was identified in exon VIII of the FIX gene.
  • This mutation results in an amino acid substitution (Threonine for Isoleucine at residue 397) in the FIX zymogen.
  • Activated FIXLB (FIXaLB) exhibited normal binding but significantly reduced activation rates of factor X and factor VII.

Conclusions:

  • The identified mutation is responsible for the FIXLB variant and hemophilia-B phenotype.
  • The amino acid substitution occurs near the catalytic triad of the FIX heavy chain, explaining the functional defect.
  • This study pinpoints a crucial residue in the FIX catalytic domain essential for normal factor IX activity.