GM26158
LCL from B-Lymphocyte
Description:
CENTRAL CORE DISEASE OF MUSCLE
RYANODINE RECEPTOR 1; RYR1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
CMD Specific
PIGI Consented Sample |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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LCL from B-Lymphocyte
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Race
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White
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Subject Type
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parent/child concordant pair
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Ethnicity
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Italian
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Country of Origin
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USA
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Family Member
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1
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Family History
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Y
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Relation to Proband
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proband
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Confirmation
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Molecular characterization after cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
RYR1 |
| Chromosomal Location |
19q13.2 |
| Allelic Variant 1 |
180901.0019; CENTRAL CORE DISEASE OF MUSCLE |
| Identified Mutation |
Arg4861His; Among 7 of 25 unrelated individuals with congenital myopathy-1A (CMYP1A; 117000) with central cores on muscle biopsy, Tilgen et al. (2001) identified a heterozygous c.14582G-A transition in the RYR1 gene, resulting in an arg4861-to-his (R4861H) substitution at a highly conserved residue in the C-terminal region of the protein.
In affected members of 2 unrelated families (CCD07 and CCD15) and an unrelated patient (CCD09) with CMYP1A, Monnier et al. (2001) identified a heterozygous R4861H mutation in exon 101 of the RYR1 gene. The mutation occurred de novo in patient CCD09.
Quinlivan et al. (2003) identified a de novo heterozygous R4861H mutation in exon 101 of the RYR1 gene in an 11-year-old boy (family D) with CMYP1A. Functional studies of the variant were not performed. As an infant, he had hypotonia with poor feeding. He later showed delayed motor development, inability to walk independently, congenital hip dislocation, lordosis, and upper limb involvement.
Sato et al. (2008) identified heterozygosity for the R4861H mutation in a 6-month-old Japanese boy (patient 2) with CMYP1A manifest as 'congenital neuromuscular disease with uniform type 1 fiber' (CNMDU1). He had poor sucking, muscle weakness, joint contractures, and 99.9% type 1 muscle fibers on skeletal muscle biopsy |
| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
14 YR |
| Sex |
Female |
| Racial Category |
White |
| Country |
USA |
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| Data Elements |
| Clinical Element Type: General NIGMS Catalog Remarks |
| (Baseline) |
| Mutation Information |
| Gene, variant, consequence, and exon number: |
RYR1, C.14582G>A (P.R4861H), MISSENSE, EXON 101 |
| Zygosity: |
Heterozygous |
| Age of Symptom Onset and Age at Diagnosis |
| In Utero History Information |
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| Birth History Information |
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| Dysmorphic Features |
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| Neurological Symptoms |
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| Optical and Audiological Symptoms |
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| Musculoskeletal Symptoms |
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| Developmental Milestones |
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| Gastrointestinal Symptoms |
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| Genitourinary Symptoms |
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| Respiratory and Cardiovascular Symptoms |
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| Cognitive and Behavioral Symptoms |
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| Additional Information |
| Testing Performed |
| Treatments and Assistive Devices |
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| Medications |
| Family History |
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INHERITED MUTATION FROM AFFECTED MOTHER GM26159. |
| Remarks |
Clinically affected; affected mother is GM26159. |
| Split Ratio |
1:5 |
| 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 |
- |
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