GM24268

GM24268 LCL from B-Lymphocyte

Description:

MYOPATHY, CENTRONUCLEAR, 1; CNM1
DYNAMIN 2; DNM2

Affected:

Yes

Sex:

Male

Age:

21 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

White

Ethnicity

Not Hispanic/Latino

Ethnicity

GERMAN/POLISH/ENGLISH/CZECH/IRISH/HUNGARIAN

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; able to run with both feet leaving the ground; walks without assistance greater than 10 steps; using genomic DNA, PCR was used to amplify exon 8 of the DNM2 gene; bi-directional sequence analysis was performed to evaluate for the mutation in the DNM2 gene; a heterozygous G>A nucleotide change was identified; this missense mutation leads to the replacement of the normal glutamic acid codon (GAG) with a lysine codon (AAG) at position 368 of the resultant protein GLU368LYS (E368K); unaffected father is GM23795(Lymph); unaffected mother is GM23794(Lymph); unaffected brother is GM23793(Lymph).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

Dynamin 2

Chromosomal Location

19p13.2

Allelic Variant 1

602378.0007; CENTRONUCLEAR MYOPATHY 1

Identified Mutation

GLU368LYS; In a French proband with centronuclear myopathy (160150), Bitoun et al. (2005) found an 1102G-to-A transition in exon 8 of the DNM2 gene that resulted in a glu368-to-lys amino acid substitution (E368K). The mutation occurred de novo. Tosch et al. (2006) reported this mutation in heterozygosity in a 36-year-old woman with centronuclear myopathy who presented with neonatal hypotonia, muscle weakness, and ophthalmoparesis. She also carried a heterozygous missense mutation in the myotubularin-related protein-14 gene (MTMR14; 611089.0002). Both mutations occurred de novo. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear myopathy.