GM26158

GM26158 LCL from B-Lymphocyte

Description:

CENTRAL CORE DISEASE OF MUSCLE
RYANODINE RECEPTOR 1; RYR1

Affected:

Yes

Sex:

Female

Age:

14 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
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

White

Subject Type

parent/child concordant pair

Ethnicity

Italian

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; affected mother is GM26159.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

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