Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA

Foe, Jerome R. Lo Ten; Rooimans, Martin A.; Bosnoyan-Collins, Lucine; Alon, Noa; Wijker, Mario; Parker, L.; Lightfoot, Jeff; Carreau, Madeleine; Callen, David F.; Savoia, Anna; Cheng, Ngan Ching; Berkel, Carola G.M. van; Strunk, Mark; Gille, Johan J. P.; Pals, Gerard; Kruyt, Frank A.E.; Pronk, Jan C.; Arwert, Fré; Buchwald, Manuel; Joenje, Hans

doi:10.1038/ng1196-320

Cited by 371 publications

(194 citation statements)

References 20 publications

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“…Attention has been drawn to leucine zipper motifs in the FANCA and FANCG proteins. 7,8,13 In the case of murine Fancg, this motif (a heptad repeat of leucine residues of the form L-X 6 -L) is not totally conserved (Figure 2). Interestingly, the murine protein also contains another shorter leucine zipper motif from residues 58-79 which is not totally conserved in the human protein.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

Demuth

Wlodarski

Tipping³

et al. 2000

Eur J Hum Genet

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FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families -97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype.

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Section: Discussionmentioning

confidence: 99%

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

Demuth

Wlodarski

Tipping³

et al. 2000

Eur J Hum Genet

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“…They are FANCA (chromosome 16q24.3), FANCC (9q22.3), and FANCG (9p13). [21][22][23] Although the Fanconi anemia gene products (at least the C protein) play obvious roles in the growth and differentiation of normal bone marrow (bone marrow is the only organ that universally fails in children with FA) the exact function of the protein products of these genes is unknown. In an effort to better understand the possible FA gene functions, a murine model for FA-C has been established by targeted embryonic stem-cell disruption.…”

Section: Fa and The Apoptotic Phenotypementioning

confidence: 99%

Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia

Lensch¹,

Rathbun

Olson

et al. 1999

Leukemia

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“…The underlying gene for FA-C (FAC) has been isolated and mapped to 9q22.3 (Strathdee et al 1992b,c). The gene responsible for FA-A (FAA) was isolated and mapped to 16q24.3 (Fanconi Anemia/Breast Cancer Consortium 1996; Lo Ten Foe et al 1996). The FAA gene showed no significant homology to any known genes; however, recent studies have demonstrated that (1) FAA protein binds to FAC protein (Kupfer et al 1997a) and (2) FAC protein is involved in cell cycle regulation via cyclin-dependent kinase cdc-2 (Kupfer et al 1997b;Kruyt et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients

et al. 1999

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Fanconi anemia (FA) is an autosomal recessive disorder characterized by pancytopenia, predisposition to cancers, and a diverse variety of congenital malformations. At least eight complementation groups, A through H, have been described. Recently, the FA-A gene (FAA) has been isolated, and a large number of distinct mutations reported in ethnically diverse FA-A patients. Here, we report on the mutation analysis of five FA patients by single-strand conformation polymorphism. Out of five patients, at least three were found to have mutations in the FAA gene. The first patient was a compound heterozygote with a 1-bp deletion and a single-base substitution. The second patient had a heterozygous 2-bp deletion, which introduces a premature termination codon, and the third patient had a heterozygous splice donor site mutation in intron 27. Key words IntroductionFanconi anemia (FA) is an autosomal recessive disorder characterized by pancytopenia, skin pigmentation, a high incidence of lymphoid and other cancers, and a diverse variety of congenital malformations (Alter BP 1993;Andrea et al. 1997). Cells from FA patients display chromosome instability (Liu et al. 1994), spontaneous delay and arrest in the G 2 cell cycle checkpoint (Dutrillaux et al. 1982), and increased sensitivity to DNA cross-linking agents (Strathdee et al. 1992a). At least eight complementation groups (FA-A to FA-H) have been described . Among these groups, FA-A accounted for twothirds of 47 FA patients from European and US/Canadian populations (Buchwald 1995). The underlying gene for FA-C (FAC) has been isolated and mapped to 9q22.3 (Strathdee et al. 1992b,c). The gene responsible for FA-A (FAA) was isolated and mapped to 16q24.3 (Fanconi Anemia/Breast Cancer Consortium 1996; Lo Ten Foe et al. 1996). The FAA gene showed no significant homology to any known genes; however, recent studies have demonstrated that (1) FAA protein binds to FAC protein (Kupfer et al. 1997a) and (2) FAC protein is involved in cell cycle regulation via cyclin-dependent kinase cdc-2 (Kupfer et al. 1997b;Kruyt et al. 1997). A large number of distinct mutations and polymorphisms have been reported in ethnically diverse FA-A patients (Savino et al. 1997; Levran et al. 1997), suggesting the presence of genetic heterogeneity in FA-A patients. To search for mutations in the FAA gene in five Japanese FA patients, we screened the FAA cDNAs by single-strand conformation polymorphism (SSCP) analysis. Four novel mutations and two common polymorphisms were identified in three patients. Materials and methods Patient cell linesA total of five FA cell lines were collected for this study: cell lines FA1CH (from Chiba prefecture), FA2CH (Chiba),

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Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA

Cited by 371 publications

References 20 publications

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia

Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients

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