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Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia

Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia
Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia
Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single-strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6.5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G > A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12-38 (-28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi-conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspected
methodology, childhood, pancreatic-cancer, disease, missense, xrcc9, fanconi, genes, polymerase-chain-reaction, mutations, identification, familial, mutation, chromosome-abnormalities, children, genetic variants, sequence variation, gene, protein, acute myeloid leukaemia, patient, cells, recombination, instability, fanconi anaemia group g gene, risk, complementation group, fancg, bone-marrow, time, high-risk
0007-1048
284-292
Meyer, S.
a50cd6a1-5144-4305-8293-9d31ee9a3e2a
Barber, L.M.
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White, D.J.
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Will, A.M.
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Birch, J. M.
19d652de-7c6f-43c0-8f9e-ef209e724609
Kohler, J.A.
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Ersfeld, K.
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Blom, E.
04cf38ab-4dc7-4d60-b01a-0f1a8e0cfd9d
Joenje, H.
9ef43080-7b62-463e-bf4c-4a42a041bbf8
Eden, T.O.B.
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Taylor, G.M.
ba60edfd-15af-4b76-8034-15e496f84444
Meyer, S.
a50cd6a1-5144-4305-8293-9d31ee9a3e2a
Barber, L.M.
9e8c61b5-6276-4ea2-b5aa-7facd10118a2
White, D.J.
4cba927c-a9c2-4441-b668-c5c7e8955113
Will, A.M.
55edaf4b-e2bb-4bf2-8bd6-b1edc49113cf
Birch, J. M.
19d652de-7c6f-43c0-8f9e-ef209e724609
Kohler, J.A.
111509dc-ae30-457b-84eb-9a4c1bb9bb39
Ersfeld, K.
bf3843c5-1238-48a5-b71b-c2ebdb2d2506
Blom, E.
04cf38ab-4dc7-4d60-b01a-0f1a8e0cfd9d
Joenje, H.
9ef43080-7b62-463e-bf4c-4a42a041bbf8
Eden, T.O.B.
b606fff1-b349-4280-8b57-7beca40fd429
Taylor, G.M.
ba60edfd-15af-4b76-8034-15e496f84444

Meyer, S., Barber, L.M., White, D.J., Will, A.M., Birch, J. M., Kohler, J.A., Ersfeld, K., Blom, E., Joenje, H., Eden, T.O.B. and Taylor, G.M. (2006) Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia. British Journal of Haematology, 133 (3), 284-292.

Record type: Article

Abstract

Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single-strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6.5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G > A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12-38 (-28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi-conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspected

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More information

Published date: 2006
Keywords: methodology, childhood, pancreatic-cancer, disease, missense, xrcc9, fanconi, genes, polymerase-chain-reaction, mutations, identification, familial, mutation, chromosome-abnormalities, children, genetic variants, sequence variation, gene, protein, acute myeloid leukaemia, patient, cells, recombination, instability, fanconi anaemia group g gene, risk, complementation group, fancg, bone-marrow, time, high-risk

Identifiers

Local EPrints ID: 62841
URI: http://eprints.soton.ac.uk/id/eprint/62841
ISSN: 0007-1048
PURE UUID: ddc118a1-d98c-4c7d-8ae3-332fe1ca21a8

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Date deposited: 09 Sep 2008
Last modified: 13 Mar 2019 20:27

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Contributors

Author: S. Meyer
Author: L.M. Barber
Author: D.J. White
Author: A.M. Will
Author: J. M. Birch
Author: J.A. Kohler
Author: K. Ersfeld
Author: E. Blom
Author: H. Joenje
Author: T.O.B. Eden
Author: G.M. Taylor

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