GM25494
LCL from B-Lymphocyte
Description:
NEMALINE MYOPATHY - TYPE UNKNOWN
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Muscular Dystrophies
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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More than one race
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Ethnicity
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Hispanic/Latino
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Ethnicity
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Puerto Rican
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Country of Origin
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USA
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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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Clinical summary/Case history
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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 |
KLHL40 |
| Chromosomal Location |
3p22.1 |
| Allelic Variant 1 |
substitution; Nemaline Myopathy, Type Unknown |
| Identified Mutation |
c.1640G>A; p.Arg547His; Variant of Uncertain Significance |
| Remarks |
Clinically affected; muscle weakness in arms and legs; esotropia; began walking at 1.5 years of age and frequently fell in childhood; motor function achieved and maintained without assistance: holding head up, sitting, walking, difficulty climbing stairs (max achieved-4 stairs with handrail); able to run at 3 years of age but by age 13 max motor function: walking 40-50 blocks, shooting a basketball, but could not lift heavy objects; had scarlet fever around 9 years of age; at 13 years of age, skeletal system showed some muscular thinning in the upper extremities and pectoralis major, but no signs of scoliosis, kyphosis, or facial muscle weakness; significant proximal upper extremity and lower extremity weakness with some distal upper extremity weakness; mild scapular winging; Gowers' maneuver elicited; noted contracture of the Achilles' tendon bilaterally; slight steppage gait with rolling of hips to aid in lifting of feet; muscle biopsy histochemistry revealed primary myopathy, unusually mild with non-specific alterations; further evaluation of biopsy showed myofibers varied greatly in size (14u to 30u), all rounded in shape, with some smaller myofibers containing glycogen aggregates below the plasma membrane; final pathology diagnosis: skeletal muscle with changes compatible with a myopathy characterized by nemaline rods (rod body myopathy); genomic DNA sequencing revealed that subject is heterozygous for variant of unknown significance in the KLHL40 gene (c.1640G>A) predicted to result in the amino acid substitution (p.Arg547His) and expected be deleterious (SIFT, PolyPhen2, Mutation-Taster); data is available for 22 other likely benign/benign variants; family history: father (not in repository) also affected with nemaline myopathy - at 19 years of age, exhibited a similar, but better developed nemaline myopathy with smearing of Z discs and muscle weakness in upper and lower extremities. |
| 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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