| Fanconi anemia is a rare autosomal
recessive disorder characterized by congenital abnormalities,
bone marrow failure, and predisposition to acute myelogenous
leukemia and other malignancies.
Of at least eight complementation
groups (FA A-H), Mutations in FA-A account for 60-65% of
affected patients1,2). The Fanconi anemia group A
gene (FANCA) maps to chromosome 16q24.3 3). It covers
more than 80.000 bp and is divided in 43 exons4). The
gene codes for a 4.3 kb mRNA coding for a 1455 amino acid
protein. More than 100 individual mutations in the
protein-coding exons of the gene, as well as in intron
sequences, have been reported in patients suffering from the
disease 5). They include base substitutions leading
to splice-site mutations and amino acid changes as well as
deletions and insertions leading to frame shifts and
large genomic deletions affecting several exons6) .
The screening of the FANCA gene
for mutations supports the clinical diagnosis of Fanconi anemia
and enables the prenatal detection of pathogenic mutations and
detection of unaffected carriers of mutated alleles among
relatives of Fanconi anemia patients.
When suspecting Fanconi anemia
(complementation group A), we routinely amplify and sequence the
target exons 13, 27, 29, 34-38 from the genomic DNA of the
patient. This group of exons covers 67 % of reported mutations.
When these exons are free of mutations, it is possible to screen
the remaining 35 protein-coding exons of the FANCA gene for
mutations in the order of the frequency of mutations*: exons 1,
6-8, 11, 15-17, 19, 20, 32, 39, 42, 43 (25 % of reported
mutations); exons 4, 5, 9, 10, 14, 18, 22-26, 28, 40, 41 (8 % of
reported mutations; and exons 2, 3, 12, 21, 30, 31, 33 (no
mutations reported yet)5)
* The mutation frequency is
depending on the ethnic background.
1)
Levran et al. (1997) Proc. Natl. Acad. Sci. USA 94:13051-13056.
Sequence variation in the Fanconi anemia gene FAA.
2) Morgan et al. (1999) Am. J. Hum. Genet. 65:1330-1341.
High frequency of large intragenic deletions in the Fanconi
anemia group A gene.
3)Pronk et al. (1995) Nature Genet. 11:338-340.
Localization of the Fanconi anaemia complementation
group A gene to chromosome 16q24.3.
4) Ianzano et al. (1997) Genomics 41:309-314.
The genomic organization of the Fanconi anemia group A (FAA)
gene.
5) Fanconi Anemia Mutation Database, Rockefeller
University Hospital, New York.
6) Morgan et al. (1999) Am. J. Hum. Genet. 65:1330-1341.
High frequency of large intragenic deletions in the Fanconi
anemia group A gene.
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| The recommended source for
genomic DNA is EDTA-blood. A typical sample volume is 0.5 ml.
Blood samples can be send to us at ambient temperature. Other
sources may also be considered for analysis (e.g. tissue
biopsies or paraffin embedded material). |
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Please
contact us for an estimate
for the analysis of the FANCA gene of your patient.
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The screening service for FANCA is available 7 days
a week. |
| We usually provide results of the
screening of the exon-groups within 2 weeks after receipt of the
sample. |
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