GM16825
Fibroblast from Skin, Unspecified
Description:
ALEXANDER DISEASE
GLIAL FIBRILLARY ACIDIC PROTEIN; GFAP
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of the Nervous System |
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Biopsy Source
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Unspecified
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Unspecified
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Race
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White
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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 Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
GFAP |
| Chromosomal Location |
17q21 |
| Allelic Variant 1 |
137780.0001; ALEXANDER DISEASE |
| Identified Mutation |
ARG239CYS; Brenner et al. [Nature Genet. 27: 117-120 (2001)] found that 5 unrelated patients with Alexander disease (203450) were heterozygous for mutations in codon 239 of the GFAP gene. In 4 of these, a C-to-T transition at nucleotide 729 led to an arg239-to-cys mutation (R239C). Age at death in these 4 patients varied from 4 years to 11 years. |
| Remarks |
Line ALX-2; slightly floppy with poor eye contact in the first year; at 18 months increasing head size and beginning of regression. MRI at 2.5 years showed white matter deterioration and ventricular cyst; first seizure at age 3.5 years; at 5.5 years had frequent and longer seizures and swallowing difficulties; died at 6 years, 3 months of age; autopsy confirmed the diagnosis; donor subject is heterozygous for a mutation in codon 239 of the GFAP gene; a C-to-T transition at nucleotide 729 (729C>T) results in an arg239-to-cys mutation [ARG239CYS (R239C)]. |
| Li L1, Tian E2, Chen X2, Chao J2, Klein J2, Qu Q2, Sun G3, Sun G2, Huang Y2, Warden CD4, Ye P2, Feng L2, Li X2, Cui Q2, Sultan A2, Douvaras P5, Fossati V5, Sanjana NE6, Riggs AD3, Shi Y7., GFAP Mutations in Astrocytes Impair Oligodendrocyte Progenitor Proliferation and Myelination in an hiPSC Model of Alexander Disease Cell Stem Cell23:239-251 2018 |
| PubMed ID: 30075130 |
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| Kondo T, Funayama M, Miyake M, Tsukita K, Era T, Osaka H, Ayaki T, Takahashi R, Inoue H, Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes Acta neuropathologica communications4:69 2016 |
| PubMed ID: 27402089 |
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| Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A, Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet27(1):117-20 2001 |
| PubMed ID: 11138011 |
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| Messing A, Goldman JE, Johnson AB, Brenner M, Alexander disease: new insights from genetics. J Neuropathol Exp Neurol60(6):563-73 2001 |
| PubMed ID: 11398833 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Heat Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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