Gene: [16q243/FANCA] Fanconi anemia, complementation group A gene; Fanconi anemia, complementation group A; Fanconi pancytopenia, type 1; [FACA FAA FA1 ]
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PAT |
[1] Fanconi anemia is a disease characterized by bone marrow failure,
finally leading to a pancytopenia (anemia, leukopenia, and thrombo-
penia) of the peripheral blood, variable phenotypic abnormalities,
including short stature; skeletal deformities, especially of the humb
and the radius; microcephaly; microphthalmus; hypogenitalism; low birth
weight; impaired growth of the body; hyperpigmentation, and predisposi-
tion to malignancy (Fanconi-1967; Schroeder-1976). A deficiency of DNA
repair and high chromosomal instability are the features of the disease
(Schuler-1969; Sasaki-1975; Auerbach-1989; Schroder-1964;
Swift-1971).
[2] An another single gene disorder accompanied by chromosomal breakage and predisposition to leukemia is Bloom syndrome (MIM:210900). In Bloom syndrome, most interchanges are between homologous chromosomes, whereas in Fanconi anemia they are usually between nonhomologous chromosomes. [3] The onset of the disease is within the first decade of life, most frequently between the 5th and the 9th year. Usually, the course of the disease is slowly progressive. The patients die from bleeding, inter- current infections, or acute leukemia (about 10%) (Fairburn-1947; Cowdell-1955; Garriga-1959; Bloom-1966; Schroeder-1971; Swift-1972). [4] The proof of increased chromosomal instability in blood cell cultures is used presently for differential diagnosis even in the premorbid stage of the disease. [5] Cultured FA human cells demonstrate a spontaneous chromosomal instability (Schroeder-1964, Schroeder-1982), hypersensivity to the cytotoxic and clastogenic effect of crosslinking agents such as mitomycin C, diepoxybutane and photoactivated psoralens (Schuler-1969; Sasaki-1973b; Auerbach-1976; Weksberg-1979; Ishida-1982) and sensitivity to oxidative stress (Joenje-1981; Joenje-1983; Gille-1987). Cultured FA cells also exhibit a highly specific endogenous cell cycle defect: a G2 phase of about twice the normal length (Dutrillaux-1982) and anomalies in mutation frequencies and in the pattern of mutations (Papadopoulo-1990a,b). This defect is oxygen sensitive in FA fibroblasts and can be alleviated by exposure of these cells to low oxygen levels. The molecular basis for FA is unknown. No consistent enzyme defect has been identified." |
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ASS |
It was reported that the nuclear enzyme DNA topoisomerase I was abnormally distributed between cytoplasm and nuclei in placentar cells from a pregnancy with this disease (Wunder-1981,1984), however data of Auer-1982 do not agree with this." |
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PND |
Diepoxybutane-induced chromosomal breakage has been used for prenatal diagnosis of FA in cultured amniotic fluid cells (Auerbach-1976,1981,1985,1986,1989)." |
|
FOG |
Fanconi anemia is a rare autosomal recessive disease affecting all races; affected individuals are predisposed to acute myelogenous leukemia and other malignancies (Swift-1971). Some authors mentioned that the sex ratio of FA patients is shifted towards the males and the maternal age is increased (Baumann-1951; Nilsson-1960)." |
|
POP |
Because the diagnosis of FA on the basis of clinical manifestations alone can often be unreliable (Glanz-1982; Auerbach-1989), an FA carrier frequency estimate of 1:300 (Swift-1971) may be significantly lower than the true frequency." |
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LIN |
[1] FA1 is not linked with D20S17; FA1 is not linked with D20S16; FA1 is
not linked with D20S4;
FA1 is not linked with D20S25; FA1 is not linked with D20S15; FA1 is not
linked with D20S19;
FA1 is linked with D20S20 {Z-max=3.04,teta-max=0.12} (Mann-1991).
[2] FA1 is linked with D20S19 {lods=2.6,teta=0.001}{lods=2.1,teta=0.001} (admixture test) (Mann-1991). Com. An admixture test revealed significant evidence for linkage heterogeneity at the D20S19 locus. Lod scores suggestive of linkage between Fanconi anemia and this locus were obtained with two of the largest kindreds studies (lods=2.6 and 2.1, at teta=0.001) (Mann-1991). [3] Pronk-1995 concluded that the FA1 gene is not on Chr 20q13 which was excluded in their linkage studies, but rather linked to microsatellite markers on Chr 16q24.3." |
|
HET |
Previously heterogeneity of this disease has been concluded from genetic analysis, considering age of onset and severity of the panmyelopathia, which shows remarkable constancy within one sibship, but wide interfamilial variation (German-1972, Schroeder-1976). Genetic heterogeneity within FA has been recently shown by complementation analysis of somatic cell hybrids constructed from FA lymphoblastoid cell lines (Zakrzewski-1980, Duckworth-Rysiecky-1985). The presence of at least two complementation groups was demonstrated by the measurement of growth inhibition by the DNA-crosslinking agent, mitomycin C, and of spontaneous and MMC-induced chromosome breakage." |
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HIS |
See Fanconi G: Jahrb Kinderheilk, 117, 257-280, 1927. |
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REL |
GEM:00.0/FANCB; GEM:09q223/FANCC; GEM:03p25/FANCD; GEM:00.0/FANCE; GEM:00.0/FANCF; GEM:00.0/FANCG; GEM:00.0/FANCH." |
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REF |
CLO,SEQ,MUT "Anonymous: Nature Genet, 14, N3, 324-328, 1996 LOC,LIN "Arwert F &: CCG, 56, 23-26, 1991 ASS "Auer &: Hum Genet, 61, 369-371, 1982 PAT,POP,PND "Auerbach AD &: Blood, 73, 391-396, 1989a ASS,LIN "Auerbach AD &: CCG, 51, (HGM10), 954, 1989b PND "Auerbach AD &: Hum Genet, 73, 86-88, 1986 PND "Auerbach AD &: Pediatrics, 76, 794-800, 1985 PND "Auerbach AD &: Pediatrics, 67, 128-135, 1981 MEB,PND "Auerbach AD, Wolman: Nature, 261, 494-496, 1976 HIS,FOG "Baumann T: Ann Pediatr, 177, 65-76, 1951a HIS,FOG "Baumann T: Ann Pediatr, 177, 142-174, 1951b HIS,PAT "Bloom &: New Engl J Med, 274, 8-14, 1966 HIS,PAT "Cowdell &: Blood, 10, 788-801, 1955 PHE "Duckworth-Rysiecky &: Somat Cell Mol Genet, 11, 35-41, 1985 MEB "Dutrillaux &: Hum Genet, 62, 327-332, 1982 HIS,PAT "Fairburn, Burden: Brit J Cancer, 1, 352-362, 1947 HIS,PAT "Fanconi G: Semin Hematol, 4, 233-240, 1967 HIS,PAT "Garriga, Crosby: Blood, 14, 1008-1014, 1959 PHE "German J: Prog Med Genet, 8, 61-101, 1972 MEB "Gille &: Hum Genet, 77, 28-31, 1987 POP "Glanz, Fraser: J Med Genet, 19, 412-416, 1982 LIN,LOC "Gschwend M &: AJHG, 59, N2, 377-384, 1996 CLO,SEQ,GEN "Ianzano L &: Genomics, 41, N3, 309-314, 1997 MEB "Ishida R, Buchwald: Cancer Res, 42, 4000-4006, 1982 MEB "Joenje H, Oostra: Hum Genet, 65, 99-101, 1983 MEB "Joenje H &: Nature, 290, 142-143, 1981 LOC,LIN "Lee R &: CCG, 58, (HGM11), 2030-2031, 1991 CLO,SEQ,MUT "Lo Ten Foe JR &: Nature Genet, 14, N3, 320-323, 1996 LOC,LIN "Mann WR &: Genomics, 9, N2, 329-337, 1991 PHE "Moustacchi &: Hum Genet, 75, 45-47, 1987 HIS,FOG "Nilsson LR: Acta Paediatr, 49, 518-529, 1960 MEB,EXP,ASS "Papadopoulo &: Cancer Res, 50, 3289-3294, 1990a MEB,EXP,ASS "Papadopoulo &: PNAS, 87, N21, 8383-8387, 1990b LIN,LOC "Pronk JC &: Nature Genet, 11, N3, 338-340, 1995 FUN "Saito H &: Hum Genet, 93, 583-586, 1994 PAT,MEB "Sasaki &: Cancer Res, 33, 1829-1836, 1973a MEB "Sasaki, Tonomura: Cancer Res, 33, 1829-1836, 1973b MUT "Savino M &: AJHG, 61, N6, 1246-1253, 1997 MEB "Schroeder &: CCG, 13, (HGM1), 119-132, 1982 PAT,PHE,FOG "Schroeder &: Hum Genet, 32, 257-288, 1976 PAT "Schroeder &: Blood, 37, 96-112, 1971 MEB "Schroeder &: Humangenetik, 1, 194-196, 1964 PAT,MEB "Schuler &: Humangenetik, 7, 314-322, 1969 LOC,LIN "Steinlein O &: Hum Mol Genet, 1, 325-329, 1992 PAT "Swift M: Science, 178, 308-310, 1972 PAT,FOG,POP "Swift M: Nature, 230, 370-373, 1971 MEB "Weksberg &: J Cell Physiol, 101, 311-324, 1979 ASS "Wunder E: Hum Genet, 68, 276-281, 1984 ASS "Wunder E &: Hum Genet, 58, 149-155, 1981 PHE "Zakrzewski, Sperling: Hum Genet, 56, 85-88, 1980 |
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KEY |
hem, devd |
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CLA |
coding, basic |
|
LOC |
16 q24.3 |
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MIM |
MIM: 227650 |
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SYN |
FACA FAA FA1 |
