NA16633
DNA from Fibroblast
Description:
FANCONI ANEMIA, COMPLEMENTATION GROUP D2; FANCD2
FANCD2 GENE; FANCD2
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Class |
Syndromes with Increased Chromosome Breakage |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
DNA from Fibroblast
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| PDL at Freeze |
5.93 |
| Passage Frozen |
3 |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
| |
| 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). |
| |
| 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). |
| Remarks |
Clinically affected; café au lait spots; thrombocytopenia, anemia, and leukopenia at age 5; bleeding at age 7; MMC and DEB sensitivity; chromosome instability; 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; line PD20 hygro; complementation group D2; hygromycin resistant; immortalized fibroblast line; corrected version of this line is GM16634; 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 |
| |
| 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 |
| |
| Spardy N, Duensing A, Charles D, Haines N, Nakahara T, Lambert PF, Duensing S, The human papillomavirus type 16 E7 oncoprotein activates the Fanconi anemia (FA) pathway and causes accelerated chromosomal instability in FA cells Journal of virology81:13265-70 2007 |
| PubMed ID: 17898070 |
|
|