GM25161

GM25161 LCL from B-Lymphocyte

Description:

NEMALINE MYOPATHY 2, AUTOSOMAL RECESSIVE; NEM2
NEBULIN; NEB

Affected:

Yes

Sex:

Female

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Muscular Dystrophies
CMD Specific
PIGI Consented Sample

Class

Congenital Muscle Diseases

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

More than one race

Ethnicity

Not Hispanic/Latino

Ethnicity

Filipino, German, Portuguese, Scottish

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; diagnosed at age 7; symptom onset age 5-6 years; high-arched palate; scoliosis; generalized muscle weakness; respiratory insufficiency especially at night; fatigue;; muscle biopsy revealed nemaline myopathy; congenital myopathy testing via ACTA1 and NEB Gene sequencing revealed: heterozygous in exon 170 of the NEB gene for a sequence variant defined as c.24218C>A, which is predicted to result in premature protein termination (p.Ser8073*) and heterozygous in triplicated region of the NEB gene for a sequence variant defined as c.13059+5G>A; affected twin brother (not in repository) tested positive for both mutations; mother is unaffected carrier (GM25160).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

NEB

Chromosomal Location

2q23.3

Allelic Variant 1

p.Ser8073*; NEMALINE MYOPATHY 2 (NEM2)

Identified Mutation

c.24218 C>A; Nebulin is a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein and its size varies from 600 to 800 kD in a manner that is tissue-, species-, and developmental stage-specific (Stedman et al., 1988). A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs (Pelin et al., 1999).

Gene

NEB

Chromosomal Location

2q23.3

Allelic Variant 1

c.13059+5G>A; NEMALINE MYOPATHY 2 (NEM2)

Identified Mutation

c.13059+5G>A; Nebulin is a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein and its size varies from 600 to 800 kD in a manner that is tissue-, species-, and developmental stage-specific (Stedman et al., 1988). A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs (Pelin et al., 1999).