Description:
FANCONI ANEMIA, COMPLEMENTATION GROUP D2; FANCD2
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Engineered Cell Cultures |
| Class |
Syndromes with Increased Chromosome Breakage |
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Cell Type
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Microcell hybrid
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Transformant
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Untransformed
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Family Member
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1
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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 |
FANCD2 |
| Chromosomal Location |
3p25.3 |
| Allelic Variant 1 |
227646.0002; FANCONI ANEMIA, COMPLEMENTATION GROUP D2 |
| Identified Mutation |
SER126GLY AND 13-BP INS; In the PD20 cell line from a family with Fanconi anemia complementation group D2, Timmers et al. (Molec Cell 7:241-248, 2001) identified an A-to-G transition at nucleotide 376 of the FANCD2 gene, resulting in a ser126-to-gly substitution. The mutation also resulted in abnormal splicing and the insertion of 13 bp from intron 5 into the mRNA via the utilization of a cryptic splice site. Forty-three of 43 (100%) independently cloned RT-PCR products with this mutation contained this insertion, whereas only 1 of 31 (3%) control cDNA clones displayed misspliced mRNA. The 13-bp insertion generated a frameshift and predicts a severely truncated protein of 180 amino acids. The mutation was not a common polymorphism and was inherited from the mother. The paternal mutation identified in this family was an arg1236-to-his substitution (227646.0001). |
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| Gene |
FANCD2 |
| Chromosomal Location |
3p25.3 |
| Allelic Variant 2 |
227646.0001; FANCONI ANEMIA, COMPLEMENTATION GROUP D2 |
| Identified Mutation |
ARG1236HIS; In the PD20 cell line from a family with Fanconi anemia complementation group D2, Timmers et al. (Molec Cell 7:241-248, 2001) identified a G-to-A transition at nucleotide 3707 of the FANCD2 gene, resulting in an arg1236-to-his substitution. The mutation was not a common polymorphism and was inherited from the father. The maternal mutation identified in this family was an A-to-G transition at nucleotide 376 (227646.0002). |
| Remark |
Clinically affected; line PD20-3-15; corrected complementation group D2; neoresistant; no longer any sensitivity to clastogens; café au lait spots; thrombocytopenia, anemia, and leukopenia at age 5; bleeding at age 7; donor subject is a compound heterozygote: one allele has an A>G transition at nucleotide 376 of the FANCD2 gene [376A>G] resulting in a substitution of glycine for serine at codon 126 as well as abnormal splicing and the insertion of 13 bp from intron 5 into the mRNA via the utilization of a cryptic splice site [Ser126Gly (S126G) and 13-bp INS], and a second allele has a G>A transition at nucleotide 3707 of the FANCD2 gene [3707G>A] resulting in a substitution of histidine for arginine at codon 1236 [Arg1236His (R1236H)]; affected sibling; immortalized fibroblast line from this donor subject is GM16633; uncorrected lymphoblast line is GM16756. |
| Umansky C, Morellato AE, Rieckher M, Scheidegger MA, Martinefski MR, Fernández GA, Pak O, Kolesnikova K, Reingruber H, Bollini M, Crossan GP, Sommer N, Monge ME, Schumacher B, Pontel LB, Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity Nature communications13:745 2020 |
| PubMed ID: 35136057 |
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| Castillo P, Bogliolo M, Surralles J, Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage DNA repair10:518-25 2010 |
| PubMed ID: 21466974 |
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| Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M, Positional cloning of a novel Fanconi anemia gene, FANCD2. Mol Cell7(2):241-8 2001 |
| PubMed ID: 11239453 |
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| Whitney M, Thayer M, Reifsteck C, Olson S, Smith L, Jakobs PM, Leach R, Naylor S, Joenje H, Grompe M, Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p. Nat Genet11:341-3 1995 |
| PubMed ID: 7581463 |
| Split Ratio |
1:8 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
MEM (Eagle) Alpha Modification with nucleosides with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
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