Description:
FANCONI ANEMIA, COMPLEMENTATION GROUP C; FANCC
FANCC GENE; FANCC
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities
GeT-RM Samples |
| Class |
Syndromes with Increased Chromosome Breakage |
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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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Race
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White
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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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ISCN
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46,XX,add(13)(q34)[2]/46,XX,add(21)(q22)[2]/46,XX[15]
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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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| PDL at Freeze |
5.1 |
| Passage Frozen |
17 |
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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 and by Chromosome Analysis |
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| MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
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| Gene |
FANCC |
| Chromosomal Location |
9q22.3 |
| Allelic Variant 1 |
227645.0003; FANCONI ANEMIA, COMPLEMENTATION GROUP C |
| Identified Mutation |
IVS,A>T,+4; Using reverse transcription PCR and chemical mismatch cleavage (CMC), Whitney et al. (Nat Genet 4:202-205, 1993) demonstrated homozygosity for an identical splice mutation in 2 Ashkenazi Jewish patients with Fanconi anemia. Three additional patients bearing this allele were found through screening 21 other families. A single base change in the fourth intronic base changed the sequence from a consensus A to T, resulting in deletion of the 111-bp exon 4. They referred to the allele as IVS4+4, A-to-T. |
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| Gene |
FANCC |
| Chromosomal Location |
9q22.3 |
| Allelic Variant 2 |
227645.0003; FANCONI ANEMIA, COMPLEMENTATION GROUP C |
| Identified Mutation |
IVS,A>T,+4; Using reverse transcription PCR and chemical mismatch cleavage (CMC), Whitney et al. (Nat Genet 4:202-205, 1993) demonstrated homozygosity for an identical splice mutation in 2 Ashkenazi Jewish patients with Fanconi anemia. Three additional patients bearing this allele were found through screening 21 other families. A single base change in the fourth intronic base changed the sequence from a consensus A to T, resulting in deletion of the 111-bp exon 4. They referred to the allele as IVS4+4, A-to-T. |
| Remarks |
Clinically affected; complementation group C; pancytopenia; classical symptoms; increased incidence of chromatid breaks and gaps following x-irradiation during G2; low-normal NAD+ levels in cells: 973 +/- 454 pmol/million cells (mean for normal cells = 1,140 +/- 304 pmol/million cells); donor subject is homozygous for a splice site mutation [IVS4+4A>T] in the FANCC gene in which a single base change in the fourth intronic base changes the sequence from a consensus A to T, resulting in deletion of the 111-bp exon 4; see GM13136 SV40 Transformed Fibroblast.
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| Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009 |
| PubMed ID: 19815695 |
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| Ruppitsch W, Meisslitzer C, Weirich-Schwaiger H, Klocker H, Scheidereit C, Schweiger M, Hirsch-Kauffmann M, The role of oxygen metabolism for the pathological phenotype of Fanconi anemia. Hum Genet99:710-9 1997 |
| PubMed ID: 9187662 |
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| Parshad R, Sanford KK, Jones GM, Chromatid damage after G2 phase x-irradiation of cells from cancer-prone individuals implicates deficiency in DNA repair. Proc Natl Acad Sci U S A80:5612-6 1983 |
| PubMed ID: 6577447 |
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| Berger NA, Berger SJ, Catino DM, Abnormal NAD+ levels in cells from patients with Fanconi's anaemia. Nature299:271-3 1982 |
| PubMed ID: 6810184 |
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| Seres DS, Fornace AJ Jr, Normal response of fanconi's anemia cells to high concentrations of O2 as determined by alkaline elution. Biochim Biophys Acta698:237-42 1982 |
| PubMed ID: 7138867 |
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| Day, Human tumor cell strains defective in the repair of alkylation damage. Carcinogenesis1:21 (1980):237-42 1980 |
| PubMed ID: 7138867 |
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| Lubiniecki AS, Blattner WA, Dosik H, Sun C, Fraumeni JF Jr, SV40 T-antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of Fanconi anemia. Am J Hematol2:33-40 1977 |
| PubMed ID: 194477 |
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| Latt SA, Stetten G, Juergens LA, Buchanan GR, Gerald PS, Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia. Proc Natl Acad Sci U S A72:4066-70 1975 |
| PubMed ID: 1060089 |
| Passage Frozen |
17 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| 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 Not inactivated |
| Supplement |
- |
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