GM08106
LCL from B-Lymphocyte
Description:
MATURITY-ONSET DIABETES OF THE YOUNG, TYPE I; MODY1
HEPATOCYTE NUCLEAR FACTOR 4-ALPHA; HNF4A
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Maturity-Onset Diabetes of the Young |
| Class |
Other Disorders of Known Biochemistry |
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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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White
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Country of Origin
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USA
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Family Member
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34
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Family History
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Y
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Relation to Proband
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brother
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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 MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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| Gene |
HNF4A |
| Chromosomal Location |
20q12-q13.1 |
| Allelic Variant 1 |
600281.0001; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE I; MODY1 |
| Identified Mutation |
GLN268TER; In the historic R-W pedigree in which Fajans (1989) defined type 1 maturity-onset diabetes of the young (MODY1; 125850), Yamagata et al. (1996) found a a C-to-T substitution in codon 268 of the TCF14 gene that generated a CAG-to-TAG (Q268X) nonsense mutation. Some subjects in the R-W pedigree had inherited the Q268X mutation but were not yet diabetic; in addition, there were subjects in the pedigree who had noninsulin-dependent diabetes mellitus but did not inherit the Q268X mutation or at-risk haplotype. In one case, NIDDM had been diagnosed at the age of 48 years, and the patient was hyperinsulinemic, indicating that this was probably late-onset NIDDM rather than MODY. The patient had 6 children, 1 of whom also had NIDDM; another child had impaired glucose tolerance, and all had only normal alleles at the TCF14 locus.
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| Remarks |
Clinically affected with MODY; diagnosed at age 21; fasting hyperglycemia; donor subject has a C>T substitution at codon 268 in exon 7 of the HNF4A (TCF14) gene that results in a CAG>TAG nonsense mutation [Gln268Ter (Q268X)]; donor subject also has a missense polymorphism of the HNF4A (TCF14) gene: a C>T transition at nucleotide 609 in exon 4 (609C>T) resulting in a threonine to isoleucine change at codon 130 [Thr130Ile (T130I)]; brother of proband GM01237; son of GM10036; father of GM08107, GM11452, GM11493, and GM11494; spouse of GM11453; extended pedigree available in PMID:102555. |
| Petrovick MS, Boettcher T, Fremont-Smith P, Peragallo C, Ricke DO, Watkins J, Schwoebel E, Analysis of complex DNA mixtures using massively parallel sequencing of SNPs with low minor allele frequencies Forensic science international Genetics46:102234 2019 |
| PubMed ID: 32018060 |
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| Shaw SY, Blodgett DM, Ma MS, Westly EC, Clemons PA, Subramanian A, Schreiber SL, Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes Proceedings of the National Academy of Sciences of the United States of America46:102234 2010 |
| PubMed ID: 21183721 |
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| Herman WH, Fajans SS, Smith MJ, Polonsky KS, Bell GI, Halter JB, Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene. Diabetes46:1749-54 1997 |
| PubMed ID: 9356021 |
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| Ting CN, Burgess DL, Chamberlain JS, Keith TP, Falls K, Meisler MH, Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics16:698-706 1993 |
| PubMed ID: 8325643 |
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| Bell GI, Xiang KS, Newman MV, Wu SH, Wright LG, Fajans SS, Spielman RS, Cox NJ, Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci U S A88:1484-8 1991 |
| PubMed ID: 1899928 |
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| Fajans SS, Maturity-onset diabetes of the young (MODY). Diabetes Metab Rev5:579-606 1989 |
| PubMed ID: 2689121 |
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| Fajans SS, Cloutier MC, Crowther RL, The Banting Memorial Lecture 1978. Clinical and etiologic heterogeneity of idiopathic diabetes mellitus. Diabetes27:1112-25 1978 |
| PubMed ID: 102555 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| 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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