Coriell Institute for Medical Research
Coriell Institute of Medical Research
  • Request a Quote
  • Donate
  • Login
  • View Cart
Sample Catalog | Custom Services | Core Facilities | Genomic Data Search
  • Biobank
    • NIGMS
    • NINDS
    • NIA
    • NHGRI
    • NEI
    • Allen Cell Collection
    • Rett Syndrome iPSC Collection
    • Autism Research Resource
    • HD Community Biorepository
    • CDC Cell and DNA
    • J. Craig Venter Institute
    • Orphan Disease Center Collection
    • All Biobanks
  • Research
    • Overview
    • Meet Our Scientists
      • Our Faculty
      • Our Scientific Staff
    • Camden Cancer Research Center
    • Epigenetic Therapies SPORE
    • Core Facilities
    • Epigenomics
    • Camden Opioid Research Initiative (CORI)
    • The Issa & Jelinek Lab
    • The Jian Huang Lab
    • The Luke Chen Lab
      • The Lab
      • The Team
      • Publications
    • The Scheinfeldt Lab
    • The Shumei Song Lab
    • The Nora Engel Lab
      • The Lab
      • The Team
      • Publications
    • Publications
  • Services
    • Overview
    • Biobanking Services
      • Core Services
      • Project Management
      • Research Support Services
      • Sample Cataloging
      • Sample Collection Kits
      • Sample Data Management
      • Sample Distribution
      • Sample Management
      • Sample Procurement
      • Sample Storage
    • Bioinformatics and Biostatistics Services
    • Cellular and Molecular Services
      • Biomarker Research Solutions
      • Cell Culture
      • Nucleic Acid Isolation and Quality Control
    • Clinical Trial Support
      • Overview
      • Sample Collection
      • Data Management
      • Sample Processing and QC
      • Storage and Distribution
      • Biomarker Services
      • Data Analaysis
    • Core Facilties
      • Overview
      • Animal and Xenograft
      • Bioinformatics and Biostatistics
      • Cell Imaging
      • CRISPR Gene Engineering
      • Flow Cytometry and Cell Sorting
      • Genomics and Epigenomics
      • iPSC - Induced Pluripotent Stem Cells
      • Organoids
    • Coriell Marketplace
    • Genomic, Epigenomic and Multiomics Services
    • Stem Cells and iPSC Services
      • Core Services
      • Reprogramming
      • Characterization and Quality Control
      • Differentiated Cell Lines
      • iPSC-Derived Organoids
      • iPSC Expansion
      • iPSC Gene Editing
  • Ordering
    • Stem Cells
    • Cell Lines
    • DNA and RNA
    • Featured Products
      • FFPE
      • HMW DNA
    • Genomic Data Search
    • Search by Catalog ID
    • Help
      • Create Account
      • Order Online
      • Ordering FAQ
      • FAQs/Culture Instructions
      • Reference Materials
        • Biobanks
        • NIGMS Repository
        • NHGRI Repository
        • NINDS Repository
        • NIA Repository
        • NIST
        • GeT-RM
      • Secondary Distribution Policies
      • MTA Assurance Form
      • Shipment Policy
      • Contact Customer Service
  • About Us
    • Our History
    • Meet Our Team
    • Meet Our Board
    • Education
      • Science Fair
      • Summer Experience
      • Outreach
      • Research Program Internship
    • Press Room
      • Press Releases
      • Coriell Blog
      • Annual Report
    • Careers
      • Working at Coriell
    • Giving
      • Donate
      • Giving FAQ
    • Contact Us
    • Legal Notice
  • Login View Cart
search submit
GM26186 LCL from B-Lymphocyte

Description:

CENTRAL CORE DISEASE OF MUSCLE
RYANODINE RECEPTOR 1; RYR1

Affected:

Yes

Sex:

Female

Age:

61 YR (At Sampling)

  • Overview
  • Characterizations
  • Phenotypic Data
  • Publications
  • External Links
  • Culture Protocols

Overview

back to top
Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Muscular Dystrophies
CMD Specific
PIGI Consented Sample
Biopsy Source Peripheral vein
Cell Type B-Lymphocyte
Tissue Type Blood
Transformant Epstein-Barr Virus
Sample Source LCL from B-Lymphocyte
Race Other
Ethnicity Hispanic/Latino
Ethnicity Spanish-Mexican
Country of Origin USA
Family History Y
Relation to Proband proband
Confirmation Molecular characterization before cell line submission to CCR
Species Homo sapiens
Common Name Human
Remarks Clinically affected; diagnosis and onset of symptoms at birth; dominant disorder; sequencing of the entire RYR1 gene in the cDNA identified a single mutation, I4898T, in the C-terminal transmembrane/luminal domain of the protein; ClinVar: NM_00540.2(RYR1):c.14693T>C (p.Ile4898Thr); treatment and management with exercise; family history: proband is one of 20 affected family members, several of these family members have the same I4898T mutation; see PMID 10097181.

Characterizations

back to top
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by LINE assay
 
Gene RYR1
Chromosomal Location 19q13.2
Allelic Variant 1 180901.0012; CENTRAL CORE DISEASE
Identified Mutation ILE4898THR; In a large Mexican kindred in which all affected members through 4 generations suffered from an unusually severe, highly penetrant form of CCD (117000), Lynch et al. (1999) identified an ile4898-to-thr (I4898T) mutation in the C-terminal transmembrane region of the RYR1 protein. In 2 family members tested, malignant hyperthermia (145600) was also present. Lynch et al. (1999) noted that all previously reported RYR1 mutations had been located either in the cytoplasmic N-terminus or in a central cytoplasmic region of the protein. Introduction of the I4898T mutation into a rabbit RYR1 cDNA and expression in HEK293 cells resulted in abolition of response to the agonists halothane and caffeine. Coexpression of normal and mutant RYR1 cDNAs in a 1:1 ratio, however, produced RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca(2+) release were reduced by 67%. Binding of [3H]ryanodine indicated that the heterozygous channel was activated by Ca(2+) concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca(2+) level and a significantly reduced luminal Ca(2+) level. These data indicated a leaky channel, possibly caused by a reduction in the Ca(2+) concentration required for channel activation. Comparison with 2 other coexpressed mutant/normal channels suggested that the I4898T mutation produces one of the most abnormal RYR1 channels that had been investigated, and this level of abnormality was reflected in the severe and penetrant phenotype of affected CCD individuals in the pedigree. Avila et al. (2001) expressed the analogous rabbit mutation (I4897T) in skeletal myotubes derived from Ryr1-knockout mice. They found that homozygous expression of I4897T in myotubes resulted in a complete uncoupling of sarcolemmal excitation from voltage-gated sarcoplasmic reticulum (SR) calcium ion release without significantly altering resting cytosolic calcium ion levels, sarcoplasmic reticulum calcium ion content, or Ryr1-mediated enhancement of dihydropyridine receptor (DHPR) channel activity. Coexpression of both I4897T and wildtype Ryr1 resulted in a 60% reduction in voltage-gated SR calcium ion release, again without altering resting cytosolic calcium ion levels, SR calcium ion content, or DHPR channel activity. These findings indicated that muscle weakness suffered by individuals possessing the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR calcium ion release, rather than the expression of overactive or leaky SR calcium ion release channels. Tilgen et al. (2001) identified the I4898T mutation, resulting from a 14693T-C transition, in 3 of 25 unrelated individuals with CCD. The isoleucine residue is highly conserved and is located in the C-terminal hydrophobic membrane-spanning region of the protein.

Phenotypic Data

back to top
Remarks Clinically affected; diagnosis and onset of symptoms at birth; dominant disorder; sequencing of the entire RYR1 gene in the cDNA identified a single mutation, I4898T, in the C-terminal transmembrane/luminal domain of the protein; ClinVar: NM_00540.2(RYR1):c.14693T>C (p.Ile4898Thr); treatment and management with exercise; family history: proband is one of 20 affected family members, several of these family members have the same I4898T mutation; see PMID 10097181.

Publications

back to top
Lynch PJ, Tong J, Lehane M, Mallet A, Giblin L, Heffron JJ, Vaughan P, Zafra G, MacLennan DH, McCarthy TV, A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease Proceedings of the National Academy of Sciences of the United States of America96:4164-9 1999
PubMed ID: 10097181

External Links

back to top
Gene Cards RYR1
Gene Ontology GO:0004872 receptor activity
GO:0005219 ryanodine-sensitive calcium-release channel activity
GO:0005509 calcium ion binding
GO:0005790 smooth endoplasmic reticulum
GO:0005887 integral to plasma membrane
GO:0006812 cation transport
GO:0006816 calcium ion transport
GO:0006874 calcium ion homeostasis
GO:0006936 muscle contraction
GO:0015278 calcium-release channel activity
NCBI Gene Gene ID:6261
NCBI GTR 117000 CENTRAL CORE DISEASE OF MUSCLE; CCD
180901 RYANODINE RECEPTOR 1; RYR1
OMIM 117000 CENTRAL CORE DISEASE OF MUSCLE; CCD
180901 RYANODINE RECEPTOR 1; RYR1
Omim Description CCD
  CCO
  CENTRAL CORE DISEASE OF MUSCLE

Culture Protocols

back to top
Split Ratio 1:2
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent
Serum 15% fetal bovine serum Not Inactivated
Substrate None specified
Subcultivation Method dilution - add fresh medium
Supplement -
Pricing
Commercial/For-profit:
$373.00USD
Academic/Non-profit/Government:
$216.00USD
Add to Cart
How to Order
  • Ordering Instructions
  • MTA / Assurance Form
  • Statement of Research Intent Form
Related Products
Same Subject
  • GM29109 - Stem cell
Miscellaneous
  • DNA on Demand
  • Custom Services

Our mission is to prevent and cure disease through biomedical research.

CONTACT US

CUSTOMER SERVICE
customerservice@coriell.org (800) 752-3805 • (856) 757-4848
Subscribe to our newsletter here

Coriell Institute for Medical Research
403 Haddon Avenue Camden, NJ 08103, USA (856) 966-7377

Ⓒ 2025 Coriell Institute. All rights reserved.

  • Facebook
  • Linkedin
  • Youtube