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. |
| 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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